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REVIEW ARTICLE
From the Institute for Cell, Animal and Population
Biology, Ashworth Laboratories, The University of Edinburgh, Edinburgh,
Scotland; Cellular Allergology, Forschungszentrum Borstel, Borstel,
Germany; and Department of Dermatology, Medical University of
Lübeck, Lübeck, Germany.
Basophilic granulocytes (usually referred to as
basophils) are a small population of peripheral blood leukocytes
containing cytoplasmatic granules that stain with basophilic dyes. They
were first described in 1879 by Paul Ehrlich,1 who 1 year
earlier had found a morphologically similar cell type present in
tissues that he termed Mastzellen.2 Based on
their similarity to mast cells, basophils have often been considered
(and neglected) as minor and possibly redundant "circulating mast
cells." Like mast cells, basophils possess high-affinity
immunoglobulin (Ig) E receptors (Fc Although the phenotype of mature basophils has been extensively
studied,11,12 the early stages of basophil maturation and their relationship to other cell lineages are not well understood. Basophils, as well as mast cells, monocytes, eosinophils, and neutrophils, are thought to arise from CD34+ progenitors
found in cord blood, peripheral blood, and the bone marrow.
Basophils, in particular, have been suggested to evolve from
CD34+/IL-3R Although mast cell progenitors have been documented as a separate
lineage, eg, characterized as
CD34+/CD38+ 17 or
CD34+/c-kit+/CD13+,18
most recently a new monoclonal antibody (97A6) has been described as
specific for mature mast cells and basophils and their
progenitors.19 Monoclonal antibody 97A6 did not react with
any other hematopoietic or nonhematopoietic cell type. The epitope
recognized by 97A6 may therefore be associated with a commitment of the
CD34+ precursor to a mast cell or basophil lineage distinct
from other lineages. The possibility of a common mast cell or basophil
lineage also arises from the surprising observation that basophils with phenotypic features characteristic of mast cells (presence of tryptase,
chymase, c-kit, carboxypeptidase A) can be found in patients
with asthma, allergy, or allergic-drug reactions.20 Therefore, the currently predominant concept that mast cells and basophils originate from separate lineages17,21,22 may have to be revised.
Various protocols using different combinations of cytokines and
growth factors have been described for the in vitro cultivation of
basophils from blood or bone marrow progenitors,23-25 with
the presence of exogenous IL-3 being a common prerequisite for the successful development and maturation of basophils. Other growth factors for basophils are IL-5,26 granulocyte-macrophage
colony-stimulating factor (GM-CSF),27 transforming growth
factor- It is well established that mast cells, which are found in the
tissues in the proximity of small blood vessels and postcapillary venules, play a key role in the early phase of IgE-mediated allergic reactions.31 Unlike mast cells, which differentiate and
mature in the tissues, mature basophils are found in the circulatory system, where they constitute less than 1% of circulating leukocytes. Basophils, eosinophils, and Th2 lymphocytes are recruited to the site
of inflammation during LPRs. Because until recently specific markers
for immunohistochemical detection of basophils were not available (see
"Tools for basophil research"), the participation of basophils
during LPRs has been documented mainly by indirect means,32-34 ie, by determining the pattern of mast cell-
or basophil-specific mediators like histamine (derived from both),
prostaglandin D2 (from mast cells), or leukotriene
C4 (LTC4; from basophils). It is now
well established that basophils are rapidly recruited to the
skin,35 lung,36 or nose37 after
allergen challenge.
More recently, a better understanding of the processes leading to
inflammatory cell recruitment in LPRs has sprung up from the study of
chemokines and their receptor counterparts, identifying potentially
important new targets for the treatment of asthma and other allergic
diseases.38-40 These studies complement previous knowledge
regarding the molecules involved in basophil adhesion to the
endothelium,41-43 a critical step in the process of
extravasation. The aim of the following section is to highlight the
potential roles of basophils in LPRs. We use the new nomenclature for
chemokines proposed by the Keystone Chemokine Conference (Keystone, CO,
January 18-23, 1999).40
Several reports have pinpointed eotaxin (CCL11) and the eotaxin
receptor (CCR3) as key molecules in the selective recruitment of
eosinophils to the lung during allergic airway
inflammation,44 both in animal models45-49 and
asthmatic patients.50-53 Sensitized mice with a disrupted
eotaxin gene showed a 70% reduction in the number of eosinophils
recruited by antigen in comparison with the identically treated
wild-type mice.54 Enhanced eotaxin expression in allergic
inflammation may also account for the influx of basophils, which
strongly express CCR3 on their surface and respond to eotaxin in
vitro.10,55 In addition, human basophils also respond to other chemokines such as the CC chemokines eotaxin-2 (CCL24), RANTES,
MCP-3 (CCL7), MCP-1, and MIP-1 A further insight regarding tissue influx of basophils and their
subsequent activation is also given by the actions of hematopoietic cytokines such as IL-3, IL-5, and GM-CSF. An increased expression of
these Th2 lymphocyte-derived cytokines in allergen-induced cutaneous
LPRs in atopics was clearly demonstrated by Kay and colleagues,64 and these cytokines have also been shown to
facilitate basophil migration.65-67 In addition, IL-3,
IL-5, and GM-CSF also enhance mediator release following either
IgE-dependent stimulation or activation due to platelet-activating
factor, C5a, and C3a. Similar properties have additionally been
described for the neurotrophic cytokine NGF.68 Moreover,
increased levels of NGF have recently been reported in allergic
rhinitis69 and asthma.70
IL-3, IL-5, GM-CSF, and NGF have similar efficacies with respect to
potentiating IgE-mediated basophil histamine and LTC4 releases, and they bind to receptors of the same subfamily but, of
these, IL-3 is the most potent71 and its effects on
basophils have been appreciated for some time.72,73 In
vitro, IL-3 alone causes little mediator release by itself, with the
exception of IL-13 production in some donors. However, a short
preincubation or coculture of basophils with IL-3 causes significant
enhancement of histamine and LTC4 release to a number of
immunologic and nonimmunologic stimuli such as anti-IgE, C5a, C3a, the
eosinophil product major basic protein, and platelet-activating
factor.74-77 Moreover, studies by
Ochensberger78 demonstrate that LTC4 synthesis
in basophils primed by IL-3 before stimulation with C5a is continuously
maintained over many hours. This clearly highlights the ability of
basophils to maintain a state of activity over longer periods than
previously anticipated. Additionally, these authors showed an elevated
production of IL-4 and IL-13 from basophils under the same
conditions,78 which may exacerbate LPRs because of the
up-regulatory effects of these cytokines on vascular cell adhesion
molecule-1 (VCAM-1), thus promoting further influx of inflammatory
cells (discussed in detail below).
The ability of basophils to continuously produce LTC4 and
cytokines may also be particularly important in maintaining chronic allergic inflammatory diseases, such as asthma. Furthermore, because IL-3 can, in conjunction with C5a, cause basophil mediator release independently of IgE-receptor cross-linking, this suggests a role for
basophils in nonallergic inflammatory diseases caused by either bacterial infections or IgG immune complexes. In addition to the combined effects of C5a and IL-3, C5a by itself is a highly potent and
efficacious inducer of histamine release from basophils79 following binding to the C5a receptor, CD88.80 In
contrast, most human mast cell subtypes do not express CD88 and are
unresponsive to C5a except skin mast cells.80 Moreover,
unlike basophils, mature human mast cells, including those of the skin,
also do not express receptors for IL-3 and GM-CSF.81 This
clearly suggests that, compared with mast cells, basophils are more
sensitive to the effects of immunomodulatory cytokines and
proinflammatory factors, which are likely to be in abundance in both
LPRs and other (nonallergic) inflammatory conditions.
Unfortunately, the interplay of these various basophil activators, in
terms of the net clinical outcome of their combined effects, in
allergic disease remains to be elucidated. However, the importance of
IL-3 in vivo as both a modulator of basophil growth and activation as
well as its ability to cause clinical symptoms of allergic inflammation
was shown by van Gils et al.82 Using rhesus monkeys
treated with the IL-3, the authors observed a clear increase in both
basophil numbers together with an up-regulation of IL-3 receptors
without a concomitant rise of IL-3R+ monocytes or mast
cells.82 Moreover, the same authors also demonstrated that
IL-3 treatment caused severe hypersensitivity reactions including
urticaria, vomiting, diarrhea, edema, arthritis, and stimulation of
hemopoiesis.83 Given the above evidence, IL-3 and related
hematopoietic growth factors, as well as NGF, potentially play a
pivotal role in exacerbating LPRs in addition to CC chemokines describedearlier.
Another indirect line of evidence that reveals basophils as potential
major regulatory cells in allergic inflammation comes from the study of
their cytokine profile. As described earlier, human basophils are an
important source of the proallergic cytokines IL-4 and IL-13. Kasaian
et al84 have shown that allergen-induced IL-4 from primary
cultures of unfractionated peripheral blood leukocytes of atopic
patients is mainly basophil-derived. This finding has been confirmed
and extended to IL-13 by Devouassoux and coworkers,85 who
found that basophils are the main source of both cytokines early after
allergen stimulation of peripheral blood cells. IL-4 is of central
importance for the recruitment of inflammatory cells to the tissues,
because it induces the expression of the adhesion molecule VCAM-1 on
endothelial cells in vitro42 and it recruits eosinophils in
vivo, eg, when injected in rodents.86,87 Transgenic mice
expressing IL-4 in the lung under the control of a lung-specific
promoter showed eosinophil infiltrations in the airways.88
Recently, Hickey et al89 have used intravital microscopy to
demonstrate that the VLA (very late antigen)-4/VCAM-1 interaction is
necessary and sufficient for IL-4-induced eosinophil recruitment in
mice. On the other hand, it has been shown that IL-4, especially in
combination with tumor necrosis factor (TNF)-
Recent evidence has implicated the pleiotropic cytokine IL-13,
which is also produced in large amounts by activated basophils, as a
key mediator of allergic asthma. In humans, IL-13 is secreted following
local allergen challenge in subjects with mild atopic asthma.92 Work performed by 2 independent laboratories,
using an IL-13R-Fc fusion protein that specifically neutralizes IL-13, has indicated that this cytokine is necessary and sufficient for establishment of an asthmatic phenotype in a murine
model.93,94 Administration of soluble recombinant IL-13
was effective in inducing airway hyperresponsiveness and in generating
a significant recruitment of eosinophils to the lung, as shown by their
appearance in bronchoalveolar lavages.93 In vitro, IL-13
induces recruitment and prolongs the survival of
eosinophils,95 up-regulates VCAM-1 expression on vascular
endothelium,96 and is a very potent inducer of eotaxin in
airway epithelial cells.97 The importance of IL-13 in the pathogenesis of asthma is also corroborated by a recent study using transgenic mice that express IL-13 selectively in the
lung.98 The authors of this study found that transgenic
mice, in the absence of a specific sensitization, developed a phenotype
very similar to the asthmatic phenotype, including eosinophil
infiltration, up-regulation of eotaxin, mucus hypersecretion by goblet
cells, subepithelial airway fibrosis, and airway
hyperresponsiveness to methacholine.98
Finally, basophils have also been proposed to play a key role in
allergy by directly inducing the switch to the IgE isotype in B cells
independently of T cells (Figure 1). Gauchat et al have shown that the
basophil cell line KU812, as well as purified peripheral blood
basophils, the mast cell line HMC-1, and human lung mast cells, can
provide the necessary signals for IgE production in vitro, ie, IL-4,
IL-13, and CD40L.9 Basophils generated from human
umbilical cord blood mononuclear cells, after cultivation in the
presence of appropriate cytokines, expressed detectable levels of CD40L
and induced IgG4 and IgE synthesis in B cells when stimulated with
allergen.8 The induction of IgE synthesis was completely
abrogated by neutralizing IL-4 and IL-13 with monoclonal antibodies or
CD40L with soluble CD40.8
Taken together, the data about the involvement of IL-4, IL-13, and
eotaxin as key players in the pathogenesis of asthma, together with the
proven infiltration and activation of basophils in the tissues during
LPRs, makes it reasonable to assume that basophils, as a major source
of IL-4 and IL-13 and by constitutively expressing CCR3 and CD40L on
their surface, may play an important but underestimated role in the
pathology of asthma and other allergic conditions. The knowledge about
the relative roles and contribution of basophils, eosinophils, mast
cells, and T cells to these processes as well as about their
interplay32 is still preliminary and needs further refinement.
The effector role of basophils in IgE-mediated allergy is well
known to depend on cross-linking of Fc Early IgE-dependent signaling events in basophils
Although several of the early IgE-dependent signaling events in
basophils are known, there are currently no pharmacologic approaches to
the treatment of allergy that specifically modulate very early
signaling events following cross-linking with allergen. However, the
molecules known to be involved in early post-cross-linking are also
used by other immunoreceptor systems affecting many other immune cell
functions, thus making selective pharmacologic intervention difficult.
Therefore, an alternative strategy is to inhibit either Fc PI 3-kinase is a universal regulator of basophil mediator
release
With respect to mast cell and basophil degranulation, there is a
universal consensus that PI 3-kinase inhibitors abolish
granule-associated release.108-112 However, in regard to
LTC4 production, Marquardt et al reported that the PI
3-kinase inhibitor wortmannin had no effect on the production of the
eicosanoid in murine mast cells.109 The same authors also
failed to detect any effects of this compound on cytokine release,
whereas other reports have described inhibition of either leukotriene
synthesis or TNF- Extracellular signal-related kinases control basophil LTC4 production but not histamine or cytokine release The extracellular signal-related kinases (ERKs) consist of 2 forms, ERK-1 and ERK-2 (sometimes referred to as p44 and p42 MAP kinases), which are considerably homologous to another in both structure and function.115 ERKs are activated after Fc RI cross-linking via Vav, Ras-Raf1, and MEK1 and activate
phospholipase A2 (PLA2) as well as several
transcription factors (Figure 2). The role of ERKs in basophils,
however, has only recently been partially investigated. Studies from
our own laboratory and from Miura et al116 have shown that
ERK phosphorylation occurs within 3 to 10 minutes of basophil
stimulation, after which there is a decrease to basal levels. The MEK
inhibitor PD-098059 abolishes both anti-IgE-induced ERK activation and
LTC4 production in basophils but has little effect on
histamine release or cytokine synthesis (IL-4 and
IL-13).107,116 The above studies highlight that ERK activation does not seem to affect cytokine transcription in basophils although it is an important regulator of cJun, cFos, STAT, and other
transcription factors in diverse cell types. Therefore, in basophils
ERKs appear to be largely involved only in LTC4 production because of the activation of PLA2. Nevertheless, we have
also demonstrated that ERK activation is not by itself sufficient for leukotriene synthesis because IL-3, which strongly activates ERK in the
absence of IgE-dependent stimulation,116 is almost
ineffective at causing LTC4
release.74,107,117,118 Despite this, in combination with
anti-IgE, IL-3 leads to both a striking potentiation and prolongation
of ERK phosphorylation compared with the effects of IL-3 or anti-IgE
alone and leads to twice as much LTC4 production than
anti-IgE alone. Although activation of PLA2 is dependent on
ERK, translocation of soluble PLA2 from the cytosol to the membrane is dependent on calcium. However, studies by Krieger et
al119 and MacGlashan and Hubbard118 have shown
that the priming caused by briefly (< 15 minutes) preincubating
basophils with IL-3 neither requires extracellular calcium nor induces
calcium elevations. Taken together, these findings strongly suggest
that, despite there being an important regulatory input from both ERK phosphorylation and intracellular calcium mobilization regarding PLA2 activity, one or more additional signals, possibly
from protein kinase C (PKC)-dependent routes,120 are
vital for LTC4 synthesis in basophils.
Comparing human basophils with other rodent histamine-producing cells,
there are important differences with respect to regulation of cytokine
synthesis controlled through ERKs. For example, IgE-dependent TNF- Calcium dependence of basophil mediator secretion It has long been appreciated that basophil degranulation is strikingly reduced in the absence of extracellular calcium.121 Similarly, production of both IL-4 113,122,123 and IL-13 (B.F.G. et al, unpublished data, 1998) is just as dependent on the ion for optimum response to IgE-receptor activation. Calcium responses are in 2 phases.124 The first takes place by the release of intracellular calcium stores from the endoplasmic reticulum because of the effects of inositol 1,4,5-trisphosphate (IP3). The second phase is caused by the opening of calcium channels allowing an influx of the ion from the extracellular milieu and is modulated by cyclic adenosine monophosphate (cAMP)-elevating drugs.125 A rise in intracellular free calcium ions can be mimicked by using calcium ionophores such as A23187, which directly transport extracellular calcium into the cells, release internal stores of the ion, and evoke degranulation, eicosanoid generation, and cytokine production.In terms of IgE-dependent cytokine secretion, both IL-4 and IL-13 are
controlled by calcium-calcineurin pathways, which promote the
translocation of the transcription factor NFAT to the
nucleus.126 This pathway is blocked by macrolides such as
FK506 and cyclosporin A, which reduce both IL-4 and IL-13
synthesis.127 Additionally, the release of these cytokines
is also effectively blocked by cAMP-elevating drugs such as
theophylline or IL-4 and IL-13 are differentially controlled by IL-3 and PKC In terms of IgE-dependent stimulation of IL-4 and IL-13, there is no clear evidence of differential control regarding the production of these cytokines. However, the kinetics of their release from basophils is strikingly different, suggesting that factors other than the signaling routes already described above are involved. IL-4 is released rapidly, peaking within 4 hours of stimulation, and is accompanied in some donors by the release of preformed stores of this cytokine.6,129,130 In contrast, IL-13 is detectable in basophil supernatants beginning 2 hours after FcRI cross-linking,
and the amounts of this factor continue to rise for at least 16 hours.6 At present, the reasons for these differing
kinetics are unknown, but factors such as autocrine effects are now
being investigated.
In terms of the levels of IL-4 and IL-13 produced, there is growing evidence that signals employed by priming factors such as IL-3 favor the production of IL-13 rather than IL-4. IL-3 potentiates the IgE-dependent release of both factors but, in addition to this, Schroeder et al, as well as Redrup et al, have reported that IL-3 stimulation alone is sufficient itself to give rise to IL-13 generation without a marked increase in IL-4 production.126,127 These authors further showed that, in stark contrast to IgE signaling, this IL-3-dependent IL-13 release is insensitive to FK506, suggesting the involvement of an activatory pathway independent of calcineurin and NFAT. A further tier of differential control of IL-4 and IL-13 release is seen with respect to PKC. Following PMA-induced PKC activation in basophils, Schroeder and coworkers have reported that although messenger RNA expressions for both IL-4 and IL-13 are increased only IL-13 protein is released.126,127 It is not yet clear, however, which isozymes of PKC are involved. The same authors have shown that the selective PKC inhibitor bisindolylmaleimide II not only reverses the effects of PMA activation but potentiates the anti-IgE induced IL-4 release but not that of IL-13. Interestingly, bisindolylmaleimide II, as well as FK506, does not affect IL-3-induced secretion of IL-13, thus showing that IL-3-associated signaling in basophils diverges considerably from both calcium and PKC-sensitive routes compared with IgE-dependent pathways. Future aspects The brief summary above regarding the control of IgE signaling in basophils highlights 2 major problems for future consideration. First, functional differences exist between primary basophils and mast cells or basophil cell lines and, second, IgE-dependent signaling is greatly affected by the actions of priming factors such as IL-3. Thus, the net outcome of IgE-triggered basophil activation in vivo is likely to be modulated by varying degrees of the local concentrations of hematopoietic cytokines (such as IL-3, IL-5, and GM-CSF) as well as neurotrophic cytokines (NGF), complement factors, and histamine-releasing factors. Because basophils are geared to the rapid release of Th2-type cytokines, it would be of considerable interest to establish the concentrations of the above factors in the in vivo environment, particularly during an allergic reaction where acute (IgE-mediated) basophil activation occurs.
Although their existence has been known for more than a century,
the physiologic role of basophils in immunity remains a mystery. It is
conceivable that basophils, like eosinophils, neutrophils, macrophages,
and mast cells, fulfill important roles in innate immunity against
pathogenic organisms. Important clues could be derived from the study
of natural or experimentally induced gene deficiencies, as happened
with W/Wv c-kit-deficient mice,131 which have proven very
useful in dissecting the role of mast cells in immunity to intestinal
nematodes, or IL-3 Mast cells and basophils have been proposed to play an important role in the innate immune response to a variety of pathogens.133 For mast cells such a role is corroborated by an increasing body of evidence,133,134 whereas the current evidence for a comparable involvement of basophils is, at best, circumstantial. Such a role would require the ability of basophils to be activated in a non-antigen-specific manner. Indeed, several such non-antigen-specific stimuli, derived from various organisms, have been shown to induce mediator or cytokine release from basophils. For example, protein Fv, an endogenous Ig-binding protein released in the intestine of patients affected by viral hepatitis, as well as the HIV-1 glycoprotein gp 120 have recently been shown to induce IL-4 and IL-13 production from basophils and mast cells by binding to the VH3 region of IgE.135-137 Similarly, antigens derived from the egg stage of the parasite Schistosoma mansoni (SEA, or soluble egg antigen) induce the release of IL-4 and other mediators from basophils of nonimmune donors.138 This activation was dependent on the presence of IgE because a short incubation at low pH (under conditions that induce dissociation of IgE from its receptor)139 abrogated, whereas resensitization with purified IgE or other IgE-containing materials restored the activating effect of SEA (Falcone et al138 and K. Haisch et al, unpublished data, 2000). Furthermore, proteases secreted by the hookworm Necator americanus induce the de novo synthesis of IL-4 and IL-13 in the basophilic cell line KU812 (C. Phillips et al, unpublished data, 1999). The filarial parasite Brugia malayi strongly expresses the gene Bm-tph-1,140 which is closely related to a human IgE-dependent histamine releasing factor,141 but it is not known whether Bm-TPH-1 can also activate basophils. Finally, the recombinant form of the IgE-dependent human histamine-releasing factor induces histamine and IL-4 release from basophils. This factor, in contrast to original findings,142,143 has recently been shown to act independently of the presence of IgE and is now thought to bind to a receptor present on the surface of basophils.144 Because basophils rapidly release considerable amounts of IL-4 upon
stimulation, they may have a decisive impact on the outcome of a
primary infection by inducing T-cell differentiation to the Th2
phenotype. To the best of our knowledge, basophils are the only
leukocytes containing preformed IL-4, although in relatively small
amounts and not detected in all donors. Constitutive IL-4 expression in
unstimulated basophils has been demonstrated by intracellular cytokine
staining in saponin-permeabilized cells130 as well as by
enzyme-linked immunosorbent assay.6 Apart from basophils,
cells such as Th2 cells, NK1.1+ cells, Another line of evidence suggesting a possible role of basophils as a
source of early IL-4 comes from the study of the effects of plant
lectins on this cell type. It has long been known that lectins such as
concanavalin A can trigger degranulation and histamine release from
basophils.147,148 Using a panel of 16 plant lectins with
different carbohydrate specificities, we have recently shown that
lectins differentially induce the release of IL-4 (and IL-13) from
basophils.149 The capacity of the studied lectins to
trigger cytokine release correlated with their binding to different
myeloma IgE molecules Taken together, the observation that different classes of molecules derived from pathogens or endogenous sources can directly activate basophils independently of the presence of specific IgE on their surface fulfills the theoretical requirement for a role of this cell type in innate immunity or in bridging innate and specific immunity by skewing the differentiation of naive T cells to the Th2 phenotype. Thus, more research is needed to address the fundamental question concerning the true physiologic role of basophils in the immune system.
Investigation into the role of basophils in health and disease has previously been curtailed by the lack of suitable experimental tools. The following section, therefore, summarizes the currently available tools for basophil research. Monoclonal antibodies Because basophils are quickly recruited to the tissues in a variety of allergic diseases, monoclonal antibodies allowing specific detection of basophils by immunohistochemical staining would be a highly desirable tool, eg, for studying the relative contribution of this cell type to pathogenesis. Earlier protocols relied on the presence of FcRI and the absence of tryptase for immunohistochemical detection.156,157 It has become clear, however, that the
expression of FcRI is not restricted to mast cells and basophils,
because it can be up-regulated on other cells such as Langerhans
cells158 and other dendritic cells,159
eosinophils,160 and monocytes.161 Furthermore, the expression of tryptase cannot be used for
discrimination of mast cells from basophils, because the gene for
tryptase  is transcribed in the latter cell type162 and
is present in substantial amounts in peripheral blood basophils of
patients with asthma or other allergic diseases.20
Therefore, several laboratories have generated antibodies for specific
detection of basophils in flow cytometry or immunohistochemistry.
There are currently 3 basophil-specific monoclonal antibodies: BSP-1,
2D7, and BB-1. BSP-1 is an IgM class monoclonal antibody that
recognizes an epitope expressed on the surface of human basophils and
was originally raised against the human erythroblastic leukemia cell
line (HEL).163 It reacts with a 45-kd surface antigen on HEL cells in Western blots.163 Because of its low
sensitivity, BSP-1 is not suitable for
immunohistochemistry.164 Monoclonal antibody 2D7 is an
IgG1 The most recent addition to the pharmacopoeia is BB-1, an IgG2a monoclonal antibody that recognizes a 124- ( ± 11) kd antigen (estimated by the method of Hedrick and Smith)166 localized mainly to the secretory granules with a comparatively small expression on the surface.167 The BB-1 antigen was released upon activation with anti-IgE or the calcium ionophore A23187.167 Because the BB-1 antigen was not detected in any other cell types, the authors suggest its use as a discriminating marker of basophil activation, particularly in the tissues, where it has been successfully used for immunohistochemical detection of basophils in lung sections fixed in Carnoy's fluid.167 Cell lines Several studies have used the cell line KU812, originally established from a patient with chronic myelogenous leukemia.168 KU812 is seen as an immature basophil precursor169 and has served as a model for basophil differentiation. Several cytokines can induce its differentiation into basophil-like cells, including TNF- and IL-6,170,171
IL-3,172 and IL-4.173 As shown by Hara et
al,173 incubation of KU812 cells with IL-4 induced several changes, including a 10-fold increase of total histamine content, appearance of metachromatic staining with toluidine blue, and up-regulation of functionally active FcRI on the surface after 7 days, with increased transcription of FcRI ,  , and  chains' messenger RNA. Another cell line, termed LAMA-84, was
established in 1987 by Seigneurin et al174 and has also
been described as basophil-like.175 Kepley and
coworkers176 have recently described the in vitro
generation of fully functional basophils from cord blood. The protocol
consists in pulsing normal cord blood leukocytes with IL-3 for 3 to 4 hours and subsequently incubating them with fetal calf serum. The
resulting cells are mostly 2D7+, FcRI+,
express a series of integrins also found on normal peripheral blood
basophils (CD11b, CD18, CD29, and CD49d), and display basophil-like morphology by light or electron microscopy. Activation through the
high-affinity IgE receptor results in a time- and dose-dependent release of histamine. The use of basophil-like cell lines, however, must be cautiously examined given the fundamental differences in
morphology and function compared with primary human basophils.
Purification protocols A high degree of basophil purity is often required for functional studies with basophils, especially when mediator secretion from contaminating cells masks what is released by basophils. Pure basophil populations are also mandatory when investigating either intracellular signaling events or to exclude the possibility of priming cytokines (eg, IL-3, GM-CSF), derived from cellular contaminants, to influence basophil function. Therefore, several protocols for basophil purification have been published over the last decade (see references in Haisch et al177). When purifying basophils, one is faced with several challenges. First, the average percentage of basophils in the peripheral blood of healthy individuals is low (< 1%), which restricts the possible yield. Furthermore, a large donor variation in the proportion of basophils makes the final recovery of basophils unpredictable, especially when dealing with blood from unknown donors (ie, from buffy coats).178Most of the currently published purification techniques rely on initial
physical separation methods (density gradients or elutriation) that, by
themselves, do not reliably result in very high purity but are
successful in enriching basophils sufficiently enough for further
purification by immunoselection. Some protocols have relied on the
expression of the high-affinity receptor Fc
Taken together, the availability of effective protocols for the purification of nearly homogeneous basophils or for the generation of this cell type from peripheral blood precursors as well as the availability of monoclonal antibodies for immunohistochemical detection and of basophil-like cell lines should encourage further study of human basophil function. The development of similar tools for the study of murine basophils would be extremely useful because it would enable the research to be extended to experimental models of disease.
The authors thank Dr Martin J. Holland for critical comments and suggestions.
Submitted December 15, 1999; accepted August 4, 2000.
Supported by the Deutsche Forschungsgemeinschaft (Ha 1590/2-1 and Fa 359/1-1).
The publication costs of this article were defrayed in part by page charge payment. Therefore, and solely to indicate this fact, this article is hereby marked "advertisement" in accordance with 18 U.S.C. section 1734.
Reprints: Bernhard F. Gibbs, Department of Dermatology, Medical University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
1. Ehrlich P. Beiträge zur Kenntnis der granulierten Bindegewebszellen und der eosinophilen Leukocythen. Arch Anat Physiol.; 1879:166-169. 2. Ehrlich P. Beiträge zur Theorie und Praxis der histologischen Färbung [thesis]. Leipzig: 1878.
3.
Brunner T, Heusser CH, Dahinden CA.
Human peripheral blood basophils primed by interleukin 3 (IL-3) produce IL-4 in response to immunoglobulin E receptor stimulation.
J Exp Med.
1993;177:605-611 4. Arock M, Merle-Beral H, Dugas B, et al. IL-4 release by human leukemic and activated normal basophils. J Immunol. 1993;151:1441-1447[Abstract]. 5. Li H, Sim TC, Alam R. IL-13 released by and localized in human basophils. J Immunol. 1996;156:4833-4838[Abstract]. 6. Gibbs BF, Haas H, Falcone FH, et al. Purified human peripheral blood basophils release interleukin-13 and preformed interleukin-4 following immunological activation. Eur J Immunol. 1996;26:2493-2498[Medline] [Order article via Infotrieve].
7.
Ochensberger B, Daepp GC, Rihs S, Dahinden CA.
Human blood basophils produce interleukin-13 in response to IgE-receptor-dependent and -independent activation.
Blood.
1996;88:3028-3037 8. Yanagihara Y, Kajiwara K, Basaki Y, et al. Cultured basophils but not cultured mast cells induce human IgE synthesis in B cells after immunologic stimulation. Clin Exp Immunol. 1998;111:136-143[Medline] [Order article via Infotrieve]. 9. Gauchat JF, Henchoz S, Mazzei G, et al. Induction of human IgE synthesis in B cells by mast cells and basophils. Nature. 1993;365:340-343[Medline] [Order article via Infotrieve]. 10. Uguccioni M, Mackay CR, Ochensberger B, et al. High expression of the chemokine receptor CCR3 in human blood basophils. Role in activation by eotaxin, MCP-4, and other chemokines. J Clin Invest. 1997;100:1137-1143[Medline] [Order article via Infotrieve]. 11. Valent P. The phenotype of human eosinophils, basophils, and mast cells. J Allergy Clin Immunol. 1994;94(suppl):1177-1183[Medline] [Order article via Infotrieve]. 12. Valent P. Immunophenotypic characterization of human basophils and mast cells. Chem Immunol. 1995;61:34-48[Medline] [Order article via Infotrieve].
13.
Boyce JA, Friend D, Matsumoto R, Austen KF, Owen WF.
Differentiation in vitro of hybrid eosinophil/basophil granulocytes: autocrine function of an eosinophil developmental intermediate.
J Exp Med.
1995;182:49-57
14.
Leary AG, Ogawa M.
Identification of pure and mixed basophil colonies in culture of human peripheral blood and marrow cells.
Blood.
1984;64:78-83
15.
Denburg JA, Telizyn S, Messner H, et al.
Heterogeneity of human peripheral blood eosinophil-type colonies: evidence for a common basophil-eosinophil progenitor.
Blood.
1985;66:312-318 16. Weil SC, Hrisinko MA. A hybrid eosinophilic-basophilic granulocyte in chronic granulocytic leukemia. Am J Clin Pathol. 1987;87:66-70[Medline] [Order article via Infotrieve].
17.
Kempuraj D, Saito H, Kaneko A, et al.
Characterization of mast cell-committed progenitors present in human umbilical cord blood.
Blood.
1999;93:3338-3346
18.
Kirshenbaum AS, Goff JP, Semere T, Foster B, Scott LM, Metcalfe DD.
Demonstration that human mast cells arise from a progenitor cell population that is CD34(+), c-kit(+), and expresses aminopeptidase N (CD13).
Blood.
1999;94:2333-2342
19.
Buhring HJ, Simmons PJ, Pudney M, et al.
The monoclonal antibody 97A6 defines a novel surface antigen expressed on human basophils and their multipotent and unipotent progenitors.
Blood.
1999;94:2343-2356
20.
Li L, Li Y, Reddel SW, et al.
Identification of basophilic cells that express mast cell granule proteases in the peripheral blood of asthma, allergy, and drug-reactive patients.
J Immunol.
1998;161:5079-5086 21. Agis H, Willheim M, Sperr WR, et al. Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly-, CD14-, CD17-, colony-forming cell. J Immunol. 1993;151:4221-4227[Abstract]. 22. Agis H, Beil WJ, Bankl HC, et al. Mast cell-lineage versus basophil lineage involvement in myeloproliferative and myelodysplastic syndromes: diagnostic role of cell-immunophenotyping. Leuk Lymphoma. 1996;22:187-204[Medline] [Order article via Infotrieve]. 23. Kishi K, Takahashi M, Aoki S, et al. [A new Ph1 positive cell line (KU812) from a patient with blastic crisis of chronic myelogenous leukemia]. Nippon Ketsueki Gakkai Zasshi. 1984;47:709-718[Medline] [Order article via Infotrieve]. 24. Kirshenbaum AS, Goff JP, Kessler SW, Mican JM, Zsebo KM, Metcalfe DD. Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells. J Immunol. 1992;148:772-777[Abstract].
25.
Saito H, Hatake K, Dvorak AM, et al.
Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.
Proc Natl Acad Sci U S A.
1988;85:2288-2292
26.
Denburg JA, Silver JE, Abrams JS.
Interleukin-5 is a human basophilopoietin: induction of histamine content and basophilic differentiation of HL-60 cells and of peripheral blood basophil-eosinophil progenitors.
Blood.
1991;77:1462-1468 27. Yamaguchi M, Hirai K, Morita Y, et al. Hemopoietic growth factors regulate the survival of human basophils in vitro. Int Arch Allergy Immunol. 1992;97:322-329[Medline] [Order article via Infotrieve].
28.
Tsuda T, Wong D, Dolovich J, Bienenstock J, Marshall J, Denburg JA.
Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation.
Blood.
1991;77:971-979
29.
Valent P, Schmidt G, Besemer J, et al.
Interleukin-3 is a differentiation factor for human basophils.
Blood.
1989;73:1763-1769 30. Iemura A, Tsai M, Ando A, Wershil BK, Galli SJ. The c-kit ligand, stem cell factor, promotes mast cell survival by suppressing apoptosis. Am J Pathol. 1994;144:321-328[Abstract].
31.
Galli SJ.
New concepts about the mast cell.
N Engl J Med.
1993;328:257-265 32. Thomas LL. Basophil and eosinophil interactions in health and disease. Chem Immunol. 1995;61:186-207[Medline] [Order article via Infotrieve]. 33. Knol EF, Mul FP, Lie WJ, Verhoeven AJ, Roos D. The role of basophils in allergic disease. Eur Respir J Suppl. 1996;22:126s-131s[Medline] [Order article via Infotrieve]. 34. Naclerio RM, Proud D, Togias AG, et al. Inflammatory mediators in late antigen-induced rhinitis. N Engl J Med. 1985;313:65-70[Abstract]. 35. Charlesworth EN, Hood AF, Soter NA, Kagey-Sobotka A, Norman PS, Lichtenstein LM. Cutaneous late-phase response to allergen. Mediator release and inflammatory cell infiltration. J Clin Invest. 1989;83:1519-1526. 36. Liu MC, Hubbard WC, Proud D, et al. Immediate and late inflammatory responses to ragweed antigen challenge of the peripheral airways in allergic asthmatics. Cellular, mediator, and permeability changes. Am Rev Respir Dis. 1991;144:51-58[Medline] [Order article via Infotrieve]. 37. Bascom R, Wachs M, Naclerio RM, Pipkorn U, Galli SJ, Lichtenstein LM. Basophil influx occurs after nasal antigen challenge: effects of topical corticosteroid pretreatment. J Allergy Clin Immunol. 1988;81:580-589[Medline] [Order article via Infotrieve]. 38. Rothenberg ME, Zimmermann N, Mishra A, et al. Chemokines and chemokine receptors: their role in allergic airway disease. J Clin Immunol. 1999;19:250-265[Medline] [Order article via Infotrieve]. 39. Nickel R, Beck LA, Stellato C, Schleimer RP. Chemokines and allergic disease. J Allergy Clin Immunol. 1999;104:723-742[Medline] [Order article via Infotrieve]. 40. Homey B, Zlotnik A. Chemokines in allergy. Curr Opin Immunol. 1999;11:626-634[Medline] [Order article via Infotrieve]. 41. Bochner BS, Sterbinsky SA, Briskin M, Saini SS, MacGlashan DW Jr. Counter-receptors on human basophils for endothelial cell adhesion molecules. J Immunol. 1996;157:844-850[Abstract]. 42. Schleimer RP, Sterbinsky SA, Kaiser J, et al. IL-4 induces adherence of human eosinophils and basophils but not neutrophils to endothelium. Association with expression of VCAM-1. J Immunol. 1992;148:1086-1092[Abstract].
43.
Bochner BS, Luscinskas FW, Gimbrone MA Jr, et al.
Adhesion of human basophils, eosinophils, and neutrophils to interleukin 1-activated human vascular endothelial cells: contributions of endothelial cell adhesion molecules.
J Exp Med.
1991;173:1553-1557 44. Corrigan CJ. Eotaxin and asthma: some answers, more questions. Clin Exp Immunol. 1999;116:1-3[Medline] [Order article via Infotrieve].
45.
Jose PJ, Griffiths-Johnson DA, Collins PD, et al.
Eotaxin: a potent eosinophil chemoattractant cytokine detected in a guinea pig model of allergic airways inflammation.
J Exp Med.
1994;179:881-887
46.
Rothenberg ME, Luster AD, Lilly CM, Drazen JM, Leder P.
Constitutive and allergen-induced expression of eotaxin mRNA in the guinea pig lung.
J Exp Med.
1995;181:1211-1216 47. Ganzalo JA, Jia GQ, Aguirre V, et al. Mouse Eotaxin expression parallels eosinophil accumulation during lung allergic inflammation but it is not restricted to a Th2-type response. Immunity. 1996;4:1-14[Medline] [Order article via Infotrieve]. 48. Griffiths-Johnson DA, Collins PD, Jose PJ, Williams TJ. Animal models of asthma: role of chemokines. Methods Enzymol. 1997;288:241-266[Medline] [Order article via Infotrieve].
49.
Humbles AA, Conroy DM, Marleau S, et al.
Kinetics of eotaxin generation and its relationship to eosinophil accumulation in allergic airways disease: analysis in a guinea pig model in vivo.
J Exp Med.
1997;186:601-612 50. Ying S, Robinson DS, Meng Q, et al. Enhanced expression of eotaxin and CCR3 mRNA and protein in atopic asthma. Association with airway hyperresponsiveness and predominant co-localization of eotaxin mRNA to bronchial epithelial and endothelial cells. Eur J Immunol. 1997;27:3507-3516[Medline] [Order article via Infotrieve]. 51. Lamkhioued B, Renzi PM, Abi-Younes S, et al. Increased expression of eotaxin in bronchoalveolar lavage and airways of asthmatics contributes to the chemotaxis of eosinophils to the site of inflammation. J Immunol. 1997;159:4593-4601[Abstract]. 52. Mattoli S, Stacey MA, Sun G, Bellini A, Marini M. Eotaxin expression and eosinophilic inflammation in asthma. Biochem Biophys Res Commun. 1997;236:299-301[Medline] [Order article via Infotrieve]. 53. Brown JR, Kleimberg J, Marini M, Sun G, Bellini A, Mattoli S. Kinetics of eotaxin expression and its relationship to eosinophil accumulation and activation in bronchial biopsies and bronchoalveolar lavage (BAL) of asthmatic patients after allergen inhalation. Clin Exp Immunol. 1998;114:137-146[Medline] [Order article via Infotrieve].
54.
Rothenberg ME, MacLean JA, Pearlman E, Luster AD, Leder P.
Targeted disruption of the chemokine eotaxin partially reduces antigen-induced tissue eosinophilia.
J Exp Med.
1997;185:785-790 55. Yamada H, Hirai K, Miyamasu M, et al. Eotaxin is a potent chemotaxin for human basophils. Biochem Biophys Res Commun. 1997;231:365-368[Medline] [Order article via Infotrieve].
56.
Dahinden CA, Geiser T, Brunner T, et al.
Monocyte chemotactic protein 3 is a most effective basophil- and eosinophil-activating chemokine.
J Exp Med.
1994;179:751-756 57. Garcia-Zepeda EA, Combadiere C, Rothenberg ME, et al. Human monocyte chemoattractant protein (MCP)-4 is a novel CC chemokine with activities on monocytes, eosinophils, and basophils induced in allergic and nonallergic inflammation that signals through the CC chemokine receptors (CCR)-2 and -3. J Immunol. 1996;157:5613-5626[Abstract]. 58. Lukacs NW, Standiford TJ, Chensue SW, Kunkel RG, Strieter RM, Kunkel SL. C-C chemokine-induced eosinophil chemotaxis during allergic airway inflammation. J Leukoc Biol. 1996;60:573-578[Abstract]. 59. Lukacs NW, Strieter RM, Warmington K, Lincoln P, Chensue SW, Kunkel SL. Differential recruitment of leukocyte populations and alteration of airway hyperreactivity by C-C family chemokines in allergic airway inflammation. J Immunol. 1997;158:4398-4404[Abstract].
60.
Gonzalo JA, Lloyd CM, Wen D, et al.
The coordinated action of CC chemokines in the lung orchestrates allergic inflammation and airway hyperresponsiveness.
J Exp Med.
1998;188:157-167
61.
Kitaura M, Suzuki N, Imai T, et al.
Molecular cloning of a novel human CC chemokine (Eotaxin-3) that is a functional ligand of CC chemokine receptor 3.
J Biol Chem.
1999;274:27975-27980
62.
Shinkai A, Yoshisue H, Koike M, et al.
A novel human CC chemokine, eotaxin-3, which is expressed in IL-4-stimulated vascular endothelial cells, exhibits potent activity toward eosinophils.
J Immunol.
1999;163:1602-1610 63. Iliopoulos O, Baroody FM, Naclerio RM, Bochner BS, Kagey-Sobotka A, Lichtenstein LM. Histamine-containing cells obtained from the nose hours after antigen challenge have functional and phenotypic characteristics of basophils. J Immunol. 1992;148:2223-2228[Abstract].
64.
Kay AB, Ying S, Varney V, et al.
Messenger RNA expression of the cytokine gene cluster, interleukin 3 (IL-3), IL-4, IL-5, and granulocyte/macrophage colony-stimulating factor, in allergen-induced late-phase cutaneous reactions in atopic subjects.
J Exp Med.
1991;173:775-778 65. Yamaguchi M, Hirai K, Shoji S, et al. Haemopoietic growth factors induce human basophil migration in vitro. Clin Exp Allergy. 1992;22:379-383[Medline] [Order article via Infotrieve]. 66. Tanimoto Y, Takahashi K, Takata M, Kawata N, Kimura I. Purification of human blood basophils using negative selection by flow cytometry. Clin Exp Allergy. 1992;22:1015-1019[Medline] [Order article via Infotrieve]. 67. Hirai K, Morita Y, Miyamoto T. Hemopoietic growth factors regulate basophil function and viability. Immunol Ser. 1992;57:587-600[Medline] [Order article via Infotrieve].
68.
Bischoff SC, Dahinden CA.
Effect of nerve growth factor on the release of inflammatory mediators by mature human basophils.
Blood.
1992;79:2662-2669 69. Sanico AM, Koliatsos VE, Stanisz AM, Bienenstock J, Togias A. Neural hyperresponsiveness and nerve growth factor in allergic rhinitis. Int Arch Allergy Immunol. 1999;118:154-158[Medline] [Order article via Infotrieve].
70.
Bonini S, Lambiase A, Angelucci F, Magrini L, Manni L, Aloe L.
Circulating nerve growth factor levels are increased in humans with allergic diseases and asthma.
Proc Natl Acad Sci U S A.
1996;93:10955-10960 71. Burgi B, Brunner T, Dahinden CA. The degradation product of the C5a anaphylatoxin C5adesarg retains basophil-activating properties. Eur J Immunol. 1994;24:1583-1589[Medline] [Order article via Infotrieve]. 72. MacDonald SM, Schleimer RP, Kagey-Sobotka A, Gillis S, Lichtenstein LM. Recombinant IL-3 induces histamine release from human basophils. J Immunol. 1989;142:3527-3532[Abstract]. 73. Kuna P, Reddigari SR, Kornfeld D, Kaplan AP. IL-8 inhibits histamine release from human basophils induced by histamine-releasing factors, connective tissue activating peptide III, and IL-3. J Immunol. 1991;147:1920-1924[Abstract].
74.
Kurimoto Y, de Weck AL, Dahinden CA.
Interleukin 3-dependent mediator release in basophils triggered by C5a.
J Exp Med.
1989;170:467-479
75.
Bischoff SC, de Weck AL, Dahinden CA.
Interleukin 3 and granulocyte/macrophage-colony-stimulating factor render human basophils responsive to low concentrations of complement component C3a.
Proc Natl Acad Sci U S A.
1990;87:6813-6817 76. Brunner T, de Weck AL, Dahinden CA. Platelet-activating factor induces mediator release by human basophils primed with IL-3, granulocyte-macrophage colony-stimulating factor, or IL-5. J Immunol. 1991;147:237-242[Abstract]. 77. Sarmiento EU, Espiritu BR, Gleich GJ, Thomas LL. IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor potentiate basophil mediator release stimulated by eosinophil granule major basic protein. J Immunol. 1995;155:2211-2221[Abstract]. 78. Ochensberger B, Tassera L, Bifrare D, Rihs S, Dahinden CA. Regulation of cytokine expression and leukotriene formation in human basophils by growth factors, chemokines and chemotactic agonists. Eur J Immunol. 1999;29:11-22[Medline] [Order article via Infotrieve]. 79. Dvorak AM, Lett-Brown M, Thueson D, Grant JA. Complement-induced degranulation of human basophils. J Immunol. 1981;126:523-528[Medline] [Order article via Infotrieve]. 80. Fureder W, Agis H, Willheim M, et al. Differential expression of complement receptors on human basophils and mast cells. Evidence for mast cell heterogeneity and CD88/C5aR expression on skin mast cells. J Immunol. 1995;155:3152-3160[Abstract]. 81. Agis H, Fureder W, Bankl HC, et al. Comparative immunophenotypic analysis of human mast cells, blood basophils and monocytes. Immunology. 1996;87:535-543[Medline] [Order article via Infotrieve].
82.
van Gils FC, van Teeffelen ME, Neelis KJ, et al.
Interleukin-3 treatment of rhesus monkeys leads to increased production of histamine-releasing cells that express interleukin-3 receptors at high levels.
Blood.
1995;86:592-597 83. van Gils FC, Mulder AH, van den Bos C, Burger H, van Leen RW, Wagemaker G. Acute side effects of homologous interleukin-3 in rhesus monkeys. Am J Pathol. 1993;143:1621-1633[Abstract].
84.
Kasaian MT, Clay MJ, Happ MP, Garman RD, Hirani S, Luqman M.
IL-4 production by allergen-stimulated primary cultures: identification of basophils as the major IL-4-producing cell type.
Int Immunol.
1996;8:1287-1297 85. Devouassoux G, Foster B, Scott LM, Metcalfe DD, Prussin C. Frequency and characterization of antigen-specific IL-4- and IL-13- producing basophils and T cells in peripheral blood of healthy and asthmatic subjects. J Allergy Clin Immunol. 1999;104:811-819[Medline] [Order article via Infotrieve]. 86. Moser R, Groscurth P, Carballido JM, et al. Interleukin-4 induces tissue eosinophilia in mice: correlation with its in vitro capacity to stimulate the endothelial cell-dependent selective transmigration of human eosinophils. J Lab Clin Med. 1993;122:567-575[Medline] [Order article via Infotrieve].
87.
Sanz MJ, Marinova-Mutafchieva L, Green P, Lobb RR, Feldmann M, Nourshargh S.
IL-4-induced eosinophil accumulation in rat skin is dependent on endogenous TNF-alpha and alpha 4 integrin/VCAM-1 adhesion pathways.
J Immunol.
1998;160:5637-5645
88.
Rankin JA, Picarella DE, Geba GP, et al.
Phenotypic and physiologic characterization of transgenic mice expressing interleukin 4 in the lung: lymphocytic and eosinophilic inflammation without airway hyperreactivity.
Proc Natl Acad Sci U S A.
1996;93:7821-7825
89.
Hickey MJ, Granger DN, Kubes P.
Molecular mechanisms underlying IL-4-induced leukocyte recruitment in vivo: a critical role for the alpha4.
J Immunol.
1999;163:3441-3448
90.
Mochizuki M, Bartels J, Mallet AI, Christophers E, Schroder JM.
IL-4 induces eotaxin: a possible mechanism of selective eosinophil recruitment in helminth infection and atopy.
J Immunol.
1998;160:60-68
91.
Devouassoux G, Metcalfe DD, Prussin C.
Eotaxin potentiates antigen-dependent basophil IL-4 production.
J Immunol.
1999;163:2877-2882 92. Kroegel C, Julius P, Matthys H, Virchow JC Jr, Luttmann W. Endobronchial secretion of interleukin-13 following local allergen challenge in atopic asthma: relationship to interleukin-4 and eosinophil counts. Eur Respir J. 1996;9:899-904[Abstract].
93.
Wills-Karp M, Luyimbazi J, Xu X, et al.
Interleukin-13: central mediator of allergic asthma.
Science.
1998;282:2258-2261
94.
Grunig G, Warnock M, Wakil AE, et al.
Requirement for IL-13 independently of IL-4 in experimental asthma.
Science.
1998;282:2261-2263 95. Luttmann W, Knoechel B, Foerster M, Matthys H, Virchow JC Jr, Kroegel C. Activation of human eosinophils by IL-13. Induction of CD69 surface antigen, its relationship to messenger RNA expression, and promotion of cellular viability. J Immunol. 1996;157:1678-1683[Abstract]. 96. Ying S, Meng Q, Barata LT, Robinson DS, Durham SR, Kay AB. Associations between IL-13 and IL-4 (mRNA and protein), vascular cell adhesion molecule-1 expression, and the infiltration of eosinophils, macrophages, and T cells in allergen-induced late-phase cutaneous reactions in atopic subjects. J Immunol. 1997;158:5050-5057[Abstract].
97.
Li L, Xia Y, Nguyen A, et al.
Effects of Th2 cytokines on chemokine expression in the lung: IL-13 potently induces eotaxin expression by airway epithelial cells.
J Immunol.
1999;162:2477-2487 98. Zhu Z, Homer RJ, Wang Z, et al. Pulmonary expression of interleukin-13 causes inflammation, mucus hypersecretion, subepithelial fibrosis, physiologic abnormalities, and eotaxin production. J Clin Invest. 1999;103:779-788[Medline] [Order article via Infotrieve]. 99. Dvorak AM. Cell biology of the basophil. Int Rev Cytol. 1998;180:87-236[Medline] [Order article via Infotrieve]. 100. Norman JC, Price LS, Ridley AJ, Koffer A. The small GTP-binding proteins, Rac and Rho, regulate cytoskeletal organization and exocytosis in mast cells by parallel pathways. Mol Biol Cell. 1996;7:1429-1442[Abstract]. 101. Kepley CL, Wilson BS, Oliver JM. Identification of the FcepsilonRI-activated tyrosine kinases Lyn, Syk, and Zap-70 in human basophils. J Allergy Clin Immunol. 1998;102:304-315[Medline] [Order article via Infotrieve]. 102. Kepley CL, Youssef L, Andrews RP, Wilson BS, Oliver JM. Syk deficiency in nonreleaser basophils. J Allergy Clin Immunol. 1999;104:279-284[Medline] [Order article via Infotrieve]. 103. Malveaux FJ, Conroy MC, Adkinson NF Jr, Lichtenstein LM. IgE receptors on human basophils. Relationship to serum IgE concentration. J Clin Invest. 1978;62:176-181.
104.
MacGlashan D Jr, McKenzie-White J, Chichester K, et al.
In vitro regulation of FcepsilonRIalpha expression on human basophils by IgE antibody.
Blood.
1998;91:1633-1643 105. MacGlashan DW Jr, Bochner BS, Adelman DC, et al. Down-regulation of Fc(epsilon)RI expression on human basophils during in vivo treatment of atopic patients with anti-IgE antibody. J Immunol. 1997;158:1438-1445[Abstract]. 106. Knol EF, Koenderman L, Mul E, Verhoeven AJ, Roos D. Differential mechanisms in the stimulus-secretion coupling in human basophils: evidence for a protein-kinase-C-dependent and a protein-kinase-C-independent route. Agents Actions. 1990;30:49-52[Medline] [Order article via Infotrieve]. 107. Gibbs BF, Grabbe J. Inhibitors of PI 3-kinase and MEK kinase differentially affect mediator secretion from immunologically activated human basophils. J Leukoc Biol. 1999;65:883-890[Abstract].
108.
Ishizuka T, Terada N, Gerwins P, et al.
Mast cell tumor necrosis factor alpha production is regulated by MEK kinases.
Proc Natl Acad Sci U S A.
1997;94:6358-6363 109. Marquardt DL, Alongi JL, Walker LL. The phosphatidylinositol 3-kinase inhibitor wortmannin blocks mast cell exocytosis but not IL-6 production. J Immunol. 1996;156:1942-1945[Abstract].
110.
Ishizuka T, Oshiba A, Sakata N, Terada N, Johnson GL, Gelfand EW.
Aggregation of the FcepsilonRI on mast cells stimulates c-Jun amino-terminal kinase activity. A response inhibited by wortmannin.
J Biol Chem.
1996;271:12762-12766 111. Ozawa K, Masujima T, Ikeda K, Kodama Y, Nonomura Y. Different pathways of inhibitory effects of wortmannin on exocytosis are revealed by video-enhanced light microscope. Biochem Biophys Res Commun. 1996;222:243-248[Medline] [Order article via Infotrieve]. 112. Suzuki M, Hirai K, Kitani S, et al. Pharmacologic study of basophil histamine release induced by monocyte chemotactic protein-1 with kinase inhibitors. Int Arch Allergy Immunol. 1996;111:18-22[Medline] [Order article via Infotrieve]. 113. Schroeder JT, Howard BP, Jenkens MK, Kagey-Sobotka A, Lichtenstein LM, MacGlashan DW Jr. IL-4 secretion and histamine release by human basophils are differentially regulated by protein kinase C activation. J Leukoc Biol. 1998;63:692-698[Abstract]. 114. Pendl GG, Prieschl EE, Thumb W, Harrer NE, Auer M, Baumruker T. Effects of phosphatidylinositol-3-kinase inhibitors on degranulation and gene induction in allergically triggered mouse mast cells. Int Arch Allergy Immunol. 1997;112:392-399[Medline] [Order article via Infotrieve]. 115. Seger R, Krebs EG. The MAPK signaling cascade. FASEB J. 1995;9:726-735[Abstract].
116.
Miura K, Schroeder JT, Hubbard WC, MacGlashan DW Jr.
Extracellular signal-regulated kinases regulate leukotriene C4 generation, but not histamine release or IL-4 production from human basophils.
J Immunol.
1999;162:4198-4206 117. Schleimer RP, Derse CP, Friedman B, et al. Regulation of human basophil mediator release by cytokines. I. Interaction with antiinflammatory steroids. J Immunol. 1989;143:1310-1317[Abstract]. 118. MacGlashan DW Jr, Hubbard WC. IL-3 alters free arachidonic acid generation in C5a-stimulated human basophils. J Immunol. 1993;151:6358-6369[Abstract]. 119. Krieger M, von Tscharner V, Dahinden CA. Signal transduction for interleukin-3-dependent leukotriene synthesis in normal human basophils: opposing role of tyrosine kinase and protein kinase. Eur J Immunol. 1992;22:2907-2913[Medline] [Order article via Infotrieve]. 120. Miura K, Hubbard WC, MacGlashan DW Jr. Phosphorylation of cytosolic phospholipase A2 by IL-3 is associated with increased free arachidonic acid generation and leukotriene C4 release in human basophils. J Allergy Clin Immunol. 1998;102:512-520[Medline] [Order article via Infotrieve]. 121. Lichtenstein LM, Osler AG. Studies on the mechanism of hypersensitivity phenomena: IX. Histamine release from human leukocytes by rageweed pollen antigen. J Exp Med. 1964;120:507-530[Abstract]. 122. Schroeder JT, MacGlashan DW Jr, Kagey-Sobotka A, White JM, Lichtenstein LM. IgE-dependent IL-4 secretion by human basophils. The relationship between cytokine production and histamine release in mixed leukocyte cultures. J Immunol. 1994;153:1808-1817[Abstract]. 123. MacGlashan D Jr. Desensitization of IgE-mediated IL-4 release from human basophils. J Leukoc Biol. 1998;63:59-67[Abstract]. 124. MacGlashan D Jr, Botana LM. Biphasic Ca2+ responses in human basophils. Evidence that the initial transient elevation associated with the mobilization of intracellular calcium is an insufficient signal for degranulation. J Immunol. 1993;150:980-991[Abstract]. 125. Botana LM, MacGlashan DW. Differential effects of cAMP-elevating drugs on stimulus-induced cytosolic calcium changes in human basophils. J Leukoc Biol. 1994;55:798-804[Abstract]. 126. Schroeder JT, MacGlashan Jr DW, Lichtenstein LM. Mechanisms and pharmacologic control of basophil-eerived IL-4 and IL-13. Int Arch Allergy Immunol. 1999;118:87-89[Medline] [Order article via Infotrieve].
127.
Redrup AC, Howard BP, MacGlashan DW Jr, Kagey-Sobotka A, Lichtenstein LM, Schroeder JT.
Differential regulation of IL-4 and IL-13 secretion by human basophils: their relationship to histamine release in mixed leukocyte cultures.
J Immunol.
1998;160:1957-1964 128. Gibbs BF, Vollrath IB, Albrecht C, Amon U, Wolff HH. Inhibition of interleukin-4 and interleukin-13 release from immunologically activated human basophils due to the actions of anti-allergic drugs. Naunyn Schmiedebergs Arch Pharmacol. 1998;357:573-578[Medline] [Order article via Infotrieve]. 129. MacGlashan DW Jr, White JM, Huang S-K, Ono SJ, Schroeder JT, Lichtenstein LM. Secretion of IL-4 from basophils. The relationship between IL-4 mRNA and protein in resting and stimulated basophils. J Immunol. 1994;152:3006-3016[Abstract]. 130. Kon OM, Sihra BS, Till SJ, Corrigan CJ, Kay AB, Grant JA. Unstimulated basophils in atopic and nonatopic subjects express intracellular interleukin-4: detection by flow cytometry. Allergy. 1998;53:891-896[Medline] [Order article via Infotrieve]. 131. Geissler EN, Ryan MA, Housman DE. The dominant-white spotting (W) locus of the mouse encodes the c-kit proto-oncogene. Cell. 1988;55:185-192[Medline] [Order article via Infotrieve]. 132. Lantz CS, Boesiger J, Song CH, et al. Role for interleukin-3 in mast-cell and basophil development and in immunity to parasites. Nature. 1998;392:90-93[Medline] [Order article via Infotrieve]. 133. Abraham SN, Arock M. Mast cells and basophils in innate immunity. Semin Immunol. 1998;10:373-381[Medline] [Order article via Infotrieve]. 134. Abraham SN, Malaviya R. Mast cells in infection and immunity. Infect Immun. 1997;65:3501-3508[Medline] [Order article via Infotrieve].
135.
Patella V, Giuliano A, Bouvet JP, Marone G.
Endogenous superallergen protein Fv induces IL-4 secretion from human Fc epsilon RI+ cells through interaction with the VH3 region of IgE.
J Immunol.
1998;161:5647-5655 136. Patella V, Giuliano A, Florio G, Bouvet JP, Marone G. Endogenous superallergen protein Fv interacts with the VH3 region of IgE to induce cytokine secretion from human basophils. Int Arch Allergy Immunol. 1999;118:197-199[Medline] [Order article via Infotrieve].
137.
Patella V, Florio G, Petraroli A, Marone G.
HIV-1 gp120 induces IL-4 and IL-13 release from human Fc epsilon RI+ cells through interaction with the VH3 region of IgE.
J Immunol.
2000;164:589-595 138. Falcone FH, Dahinden CA, Gibbs BF, et al. Human basophils release interleukin-4 after stimulation with Schistosoma mansoni egg antigen. Eur J Immunol. 1996;26:1147-1155[Medline] [Order article via Infotrieve]. 139. Pruzansky JJ, Grammer LC, Pattterson R, Roberts M. Dissociation of IgE from receptors on human basophils. I. Enhanced passive sensitization for histamine release. J.Immunol. 1983;131:1949-1953[Abstract]. 140. Gregory WF, Blaxter ML, Maizels RM. Differentially expressed, abundant trans-spliced cDNAs from larval Brugia malayi. Mol Biochem Parasitol. 1997;87:85-95[Medline] [Order article via Infotrieve].
141.
MacDonald SM, Rafnar T, Langdon J, Lichtenstein LM.
Molecular identification of an IgE-dependent histamine-releasing factor.
Science.
1995;269:688-690 142. Schroeder JT, Lichtenstein LM, MacDonald SM. Recombinant histamine-releasing factor enhances IgE-dependent IL-4 and IL-13 secretion by human basophils. J Immunol. 1997;159:447-452[Abstract]. 143. MacDonald SM. Human recombinant histamine-releasing factor. Int Arch Allergy Immunol. 1997;113:187-189[Medline] [Order article via Infotrieve]. 144. Wantke F, MacGlashan DW, Langdon JM, MacDonald SM. The human recombinant histamine releasing factor: functional evidence that it does not bind to the IgE molecule. J Allergy Clin Immunol. 1999;103:642-648[Medline] [Order article via Infotrieve]. 145. Haas H, Falcone FH, Holland MJ, et al. Early interleukin-4: its role in the switch towards a Th2 response and IgE-mediated allergy. Int Arch Allergy Immunol. 1999;119:86-94[Medline] [Order article via Infotrieve].
146.
Coffman RL, von der Weid T.
Multiple pathways for the initiation of T helper 2 (Th2) responses.
J Exp Med.
1997;185:373-375
147.
Siraganian RP, Siragania PA.
Mechanism of action of concanavalin A on human basophils.
J Immunol.
1975;114:886-893 148. Shibasaki M, Sumazaki R, Isoyama S, Takita H. Interaction of lectins with human IgE: IgE-binding property and histamine-releasing activity of twelve plant lectins. Int Arch Allergy Immunol. 1992;98:18-25[Medline] [Order article via Infotrieve]. 149. Haas H, Falcone FH, Schramm G, et al. Dietary lectins can induce in vitro release of IL-4 and IL-13 from human basophils. Eur J Immunol. 1999;29:918-927[Medline] [Order article via Infotrieve]. 150. Loukas A, Maizels RM. Helminth C-type lectins and host-parasite interactions. Parasitol Today. 2000;16:333-339[Medline] [Order article via Infotrieve]. 151. Loukas A, Mullin NP, Tetteh KK, Moens L, Maizels RM. A novel C-type lectin secreted by a tissue-dwelling parasitic nematode. Curr Biol. 1999;12:825-828.
152.
Baenziger J, Kornfeld S.
Structure of the carbohydrate units of IgE immunoglobulin. I. Over-all composition, glycopeptide isolation, and structure of the high mannose oligosaccharide unit.
J Biol Chem.
1974;249:1889-1896
153.
Baenziger J, Kornfeld S.
Structure of the carbohydrate units of IgE immunoglobulin. II. Sequence of the sialic acid -containing glycopeptides.
J Biol Chem.
1974;249:1897-1903 154. Pritchard DI, Brown A, Kasper G, et al. A hookworm allergen which strongly resembles calreticulin. Parasite Immunol. 1999;21:439-450[Medline] [Order article via Infotrieve]. 155. Krause KH, Michalak M. Calreticulin. Cell. 1997;88:439-443[Medline] [Order article via Infotrieve]. 156. Koshino T, Arai Y, Miyamoto Y, et al. Airway basophil and mast cell density in patients with bronchial asthma: relationship to bronchial hyperresponsiveness. J Asthma. 1996;33:89-95[Medline] [Order article via Infotrieve]. 157. Castells MC, Irani AM, Schwartz LB. Evaluation of human peripheral blood leukocytes for mast cell tryptase. J Immunol. 1987;138:2184-2189[Abstract].
158.
Bieber T, de la Salle H, Wollenberg A, et al.
Human epidermal Langerhans cells express the high affinity receptor for immunoglobulin E (Fc epsilon RI).
J Exp Med.
1992;175:1285-1290 159. Maurer D, Fiebiger S, Ebner C, et al. Peripheral blood dendritic cells express Fc epsilon RI as a complex composed of Fc epsilon RI alpha- and Fc epsilon RI gamma-chains and can use this receptor for IgE-mediated allergen presentation. J Immunol. 1996;157:607-616[Abstract]. 160. Gounni AS, Lamkhioued B, Ochiai K, et al. High affinity IgE receptor on eosinophils is involved in defence against parasites. Nature. 1994;367:183-186[Medline] [Order article via Infotrieve].
161.
Maurer D, Fiebiger E, Reininger B, et al.
Expression of functional high affinity immunoglobulin E receptors (Fc epsilon RI) on monocytes of atopic individuals.
J Exp Med.
1994;179:745-750 162. Xia HZ, Kepley CL, Sakai K, Chelliah J, Irani AM, Schwartz LB. Quantitation of tryptase, chymase, Fc epsilon RI alpha, and Fc epsilon RI gamma mRNAs in human mast cells and basophils by competitive reverse transcription-polymerase chain reaction. J Immunol. 1995;154:5472-5480[Abstract].
163.
Bodger MP, Mounsey GL, Nelson J, Fitzgerald PH.
A monoclonal antibody reacting with human basophils.
Blood.
1987;69:1414-1418 164. Kepley CL, Craig SS, Schwartz LB. Identification and partial characterization of a unique marker for human basophils. J Immunol. 1995;154:6548-6555[Abstract]. 165. Irani AM, Huang C, Xia HZ, et al. Immunohistochemical detection of human basophils in late-phase skin reactions. J Allergy Clin Immunol. 1998;101:354-362[Medline] [Order article via Infotrieve]. 166. Hedrick JL, Smith AJ. Size and charge isomer separation and estimation of molecular weights of proteins by disc gel electrophoresis. Arch Biochem Biophys. 1968;126:155-164[Medline] [Order article via Infotrieve]. 167. McEuen AR, Buckley MG, Compton SJ, Walls AF. Development and characterization of a monoclonal antibody specific for human basophils and the identification of a unique secretory product of basophil activation. Lab Invest. 1999;79:27-38[Medline] [Order article via Infotrieve]. 168. Kishi K. A new leukemia cell line with Philadelphia chromosome characterized as basophil precursors. Leuk Res. 1985;9:381-390[Medline] [Order article via Infotrieve]. 169. Blom T, Huang R, Aveskogh M, Nilsson K, Hellman L. Phenotypic characterization of KU812, a cell line identified as an immature human basophilic leukocyte. Eur J Immunol. 1992;22:2025-2032[Medline] [Order article via Infotrieve]. 170. Nilsson G, Carlsson M, Jones I, Ahlstedt S, Matsson P, Nilsson K. TNF-alpha and IL-6 induce differentiation in the human basophilic leukaemia cell line KU812. Immunology. 1994;81:73-78[Medline] [Order article via Infotrieve]. 171. Navarro S, Louache F, Debili N, Vainchenker W, Doly J. Autocrine regulation of terminal differentiation by interleukin-6 in the pluripotent KU812 cell line. Biochem Biophys Res Commun. 1990;169:184-191[Medline] [Order article via Infotrieve]. 172. Valent P, Besemer J, Kishi K, et al. IL-3 promotes basophilic differentiation of KU812 cells through high affinity binding sites. J Immunol. 1990;145:1885-1889[Abstract]. 173. Hara T, Yamada K, Tachibana H. Basophilic differentiation of the human leukemia cell line KU812 upon treatment with interleukin-4. Biochem Biophys Res Commun. 1998;247:542-548[Medline] [Order article via Infotrieve]. 174. Seigneurin D, Champelovier P, Mouchiroud G, et al. Human chronic myeloid leukemic cell line with positive Philadelphia chromosome exhibits megakaryocytic and erythroid characteristics. Exp Hematol. 1987;15:822-832[Medline] [Order article via Infotrieve]. 175. Blom T, Nilsson G, Sundström C, Nilsson K, Hellman L. Characterization of a human basophil-like cell line (LAMA-84). Scand J Immunol. 1996;44:54-61[Medline] [Order article via Infotrieve]. 176. Kepley CL, Pfeiffer JR, Schwartz LB, Wilson BS, Oliver JM. The identification and characterization of umbilical cord blood-derived human basophils. J Leukoc Biol. 1998;64:474-483[Abstract]. 177. Haisch K, Gibbs BF, Korber H, et al. Purification of morphologically and functionally intact human basophils to near homogeneity. J Immunol Methods. 1999;226:129-137[Medline] [Order article via Infotrieve]. 178. Gibbs BF, Noll T, Falcone FH, et al. A three-step procedure for the purification of human basophils from buffy coat blood. Inflamm Res. 1997;46:137-142[Medline] [Order article via Infotrieve]. 179. Schroeder JT, Hanrahan LRJ. Purification of human basophils using mouse monoclonal IgE. J Immunol Methods. 1990;133:269-277[Medline] [Order article via Infotrieve]. 180. Weil GJ, Leiserson WM, Chused TM. Isolation of human basophils by flow microfluorometry. J Immunol Methods. 1983;58:359-363[Medline] [Order article via Infotrieve]. 181. Mul FP, Knol EF, Roos D. An improved method for the purification of basophilic granulocytes from human blood. J Immunol Methods. 1992;149:207-214[Medline] [Order article via Infotrieve]. 182. Bjerke T, Nielsen S, Helgestad J, Nielsen BW, Schiotz PO. Purification of human blood basophils by negative selection using immunomagnetic beads. J Immunol Methods. 1993;157:49-56[Medline] [Order article via Infotrieve]. 183. Tsang S, Hayashi M, Zheng X, Campbell A, Schellenberg RR. Simplified purification of human basophils. J Immunol Methods. 2000;233:13-20[Medline] [Order article via Infotrieve]. 184. Ponath PD, Qin S, Ringler DJ, et al. Cloning of the human eosinophil chemoattractant, eotaxin. Expression, receptor binding, and functional properties suggest a mechanism for the selective recruitment of eosinophils. J Clin Invest. 1996;97:604-612[Medline] [Order article via Infotrieve].
185.
Hogaboam C, Kunkel SL, Strieter RM, et al.
Novel role of transmembrane SCF for mast cell activation and eotaxin production in mast cell-fibroblast interactions.
J Immunol.
1998;160:6166-6171 186. Gao JL, Sen AI, Kitaura M, et al. Identification of a mouse eosinophil receptor for the CC chemokine eotaxin. Biochem Biophys Res Commun. 1996;223:679-684[Medline] [Order article via Infotrieve].
187.
Kitaura M, Nakajima T, Imai T, et al.
Molecular cloning of human eotaxin, an eosinophil-selective CC chemokine, and identification of a specific eosinophil eotaxin receptor, CC chemokine receptor 3.
J Biol Chem.
1996;271:7725-7730
188.
Sallusto F, Mackay CR, Lanzavecchia A.
Selective expression of the eotaxin receptor CCR3 by human T helper 2 cells.
Science.
1997;277:2005-2007 189. Robinson DS, Hamid Q, Ying S, et al. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med. 1992;326:298-304[Abstract].
190.
Ochi H, Hirani WM, Yuan Q, Friend DS, Austen KF, Boyce JA.
T helper cell type 2 cytokine-mediated comitogenic responses and CCR3 expression during differentiation of human mast cells in vitro.
J Exp Med.
1999;190:267-280
191.
Romagnani P, De Paulis A, Beltrame C, et al.
Tryptase-chymase double-positive human mast cells express the eotaxin receptor CCR3 and are attracted by CCR3-binding chemokines.
Am J Pathol.
1999;155:1195-1204
© 2000 by The American Society of Hematology.
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  T. Ugajin, T. Kojima, K. Mukai, K. Obata, Y. Kawano, Y. Minegishi, Y. Eishi, H. Yokozeki, and H. Karasuyama Basophils preferentially express mouse mast cell protease 11 among the mast cell tryptase family in contrast to mast cells J. Leukoc. Biol., December 1, 2009; 86(6): 1417 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Chen, J. Olsen, S. Ford, S. Mirza, A. Walker, J. M. Murphy, and I. G. Young A New Isoform of Interleukin-3 Receptor {alpha} with Novel Differentiation Activity and High Affinity Binding Mode J. Biol. Chem., February 27, 2009; 284(9): 5763 - 5773. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Pecaric-Petkovic, S. A. Didichenko, S. Kaempfer, N. Spiegl, and C. A. Dahinden Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 Blood, February 12, 2009; 113(7): 1526 - 1534. [Abstract] [Full Text] [PDF]
|
|
|
|
|
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N. Spiegl, S. Didichenko, P. McCaffery, H. Langen, and C. A. Dahinden Human basophils activated by mast cell-derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid Blood, November 1, 2008; 112(9): 3762 - 3771. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Smithgall, M. R. Comeau, B.-R. Park Yoon, D. Kaufman, R. Armitage, and D. E. Smith IL-33 amplifies both Th1- and Th2-type responses through its activity on human basophils, allergen-reactive Th2 cells, iNKT and NK Cells Int. Immunol., August 1, 2008; 20(8): 1019 - 1030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kneidinger, U. Schmidt, U. Rix, K. V. Gleixner, A. Vales, C. Baumgartner, C. Lupinek, M. Weghofer, K. L. Bennett, H. Herrmann, et al. The effects of dasatinib on IgE receptor-dependent activation and histamine release in human basophils Blood, March 15, 2008; 111(6): 3097 - 3107. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Kojima, K. Obata, K. Mukai, S. Sato, T. Takai, Y. Minegishi, and H. Karasuyama Mast Cells and Basophils Are Selectively Activated In Vitro and In Vivo through CD200R3 in an IgE-Independent Manner J. Immunol., November 15, 2007; 179(10): 7093 - 7100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Obata, K. Mukai, Y. Tsujimura, K. Ishiwata, Y. Kawano, Y. Minegishi, N. Watanabe, and H. Karasuyama Basophils are essential initiators of a novel type of chronic allergic inflammation Blood, August 1, 2007; 110(3): 913 - 920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Lee and M. P. McGarry When is a mouse basophil not a basophil? Blood, February 1, 2007; 109(3): 859 - 861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. M. Tschopp, N. Spiegl, S. Didichenko, W. Lutmann, P. Julius, J. C. Virchow, C. E. Hack, and C. A. Dahinden Granzyme B, a novel mediator of allergic inflammation: its induction and release in blood basophils and human asthma Blood, October 1, 2006; 108(7): 2290 - 2299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Schober, B. Belloni, S. Lubitz, B. Eberlein-Konig, P. Bohn, Y. Saritas, J. Lintelmann, G. Matuschek, H. Behrendt, and J. Buters Organic Extracts of Urban Aerosol (<=PM2.5) Enhance rBet v 1-Induced Upregulation of CD63 in Basophils from Birch Pollen-Allergic Individuals Toxicol. Sci., April 1, 2006; 90(2): 377 - 384. [Abstract] [Full Text] [PDF]
|
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 H Agis, M-T Krauth, I Mosberger, L Mullauer, I Simonitsch-Klupp, L B Schwartz, D Printz, A Bohm, G Fritsch, H-P Horny, et al. Enumeration and immunohistochemical characterisation of bone marrow basophils in myeloproliferative disorders using the basophil specific monoclonal antibody 2D7 J. Clin. Pathol., April 1, 2006; 59(4): 396 - 402. [Abstract] [Full Text] [PDF]
|
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 Y. Arinobu, H. Iwasaki, M. F. Gurish, S.-i. Mizuno, H. Shigematsu, H. Ozawa, D. G. Tenen, K. F. Austen, and K. Akashi Developmental checkpoints of the basophil/mast cell lineages in adult murine hematopoiesis PNAS, December 13, 2005; 102(50): 18105 - 18110. [Abstract] [Full Text] [PDF]
|
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S. Hida, M. Tadachi, T. Saito, and S. Taki Negative control of basophil expansion by IRF-2 critical for the regulation of Th1/Th2 balance Blood, September 15, 2005; 106(6): 2011 - 2017. [Abstract] [Full Text] [PDF]
|
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 |
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 E. Schneider, F. Machavoine, J.-M. Pleau, A.-F. Bertron, R. L. Thurmond, H. Ohtsu, T. Watanabe, A. H. Schinkel, and M. Dy Organic cation transporter 3 modulates murine basophil functions by controlling intracellular histamine levels J. Exp. Med., August 1, 2005; 202(3): 387 - 393. [Abstract] [Full Text] [PDF]
|
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|
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 |
|
 T. Mimura, Y. Shinozaki, H. Kawasaki, and H. Iwamura JTP-27536 [(+)-1,3-Dihydroxy-2-hydroxymethylpropyl-2-ammonium 2-[(R)-3-Cyclo-hexyl-1-phenylpropyl]-1,3-dioxo-2,3-dihydro-1H-isoindole-5-carboxylate Monohydrate], a Novel Inhibitor of Immunoglobulins and Interleukin-5 with Anti-Inflammatory Properties in Mouse Allergic Dermatitis Model J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 293 - 301. [Abstract] [Full Text] [PDF]
|
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G. Monneret, R. Boumiza, S. Gravel, C. Cossette, J. Bienvenu, J. Rokach, and W. S. Powell Effects of Prostaglandin D2 and 5-Lipoxygenase Products on the Expression of CD203c and CD11b by Basophils J. Pharmacol. Exp. Ther., February 1, 2005; 312(2): 627 - 634. [Abstract] [Full Text] [PDF]
|
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M. Mack, M. A. Schneider, C. Moll, J. Cihak, H. Bruhl, J. W. Ellwart, M. P. Hogarth, M. Stangassinger, and D. Schlondorff Identification of Antigen-Capturing Cells as Basophils J. Immunol., January 15, 2005; 174(2): 735 - 741. [Abstract] [Full Text] [PDF]
|
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A. Hartnell, A. Heinemann, D. M. Conroy, R. Wait, G. J. Sturm, M. Caversaccio, P. J. Jose, and T. J. Williams Identification of Selective Basophil Chemoattractants in Human Nasal Polyps as Insulin-Like Growth Factor-1 and Insulin-Like Growth Factor-2 J. Immunol., November 15, 2004; 173(10): 6448 - 6457. [Abstract] [Full Text] [PDF]
|
|
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B. Frossi, M. De Carli, and C. Pucillo The mast cell: an antenna of the microenvironment that directs the immune response J. Leukoc. Biol., April 1, 2004; 75(4): 579 - 585. [Abstract] [Full Text] [PDF]
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B. F. Gibbs, K. E. S. Plath, H. H. Wolff, and J. Grabbe Regulation of mediator secretion in human basophils by p38 mitogen-activated protein kinase: phosphorylation is sensitive to the effects of phosphatidylinositol 3-kinase inhibitors and calcium mobilization J. Leukoc. Biol., August 1, 2002; 72(2): 391 - 400. [Abstract] [Full Text] [PDF]
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Top
Introduction
Growth and development of...
/
+
T cells, eosinophils, and mast cells also have been found to produce
IL-4 and have been considered as a cellular source of the so-called
"early IL-4."
IgE-PS, IgE-(T+H), IgE-PE, IgE-VL
monoclonal antibody that reacts with a ligand localized to the
secretory granules of human basophils.