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IMMUNOBIOLOGY
From the Department of Immunology, Windeyer Institute of
Medical Sciences, University College London, England; Department of
Internal Medicine, University of Michigan, Ann Arbor; Institute of
Molecular Genetics, Academy of Sciences of the Czech Republic, Prague;
Department of Transfusion Medicine, Kurume University, Kurume, Fukouka,
Japan; and the University of Minnesota, Minnesota Medical School,
University Hospital, Minneapolis.
CD98 is expressed on both hematopoietic and nonhematopoietic
cells and has been implicated in a variety of different aspects of cell
physiology and immunobiology. In this study, the functional interactions between CD98 and other adhesion molecules on the surface
of the promonocyte line U937 are examined by means of a quantitative
assay of cell aggregation. Several of the CD98 antibodies induced
homotypic aggregation of these cells without affecting cellular
viability or growth. Aggregation induced by CD98 antibodies could
be distinguished from that induced by CD98 is the heavy chain (85 kd) of a cell-surface
dimeric molecule found on the surface of many hematopoietic
cells.1,2 It is a type II integral membrane protein,
with a long cytoplasmic portion of 81 amino acids. Some studies have
suggested that it may act as ligand for the cell-surface lectin
galectin-3.3 CD98 is found covalently linked to 1 of
several (6 have been identified to date) alternative light chains, at
least 4 of which have been identified as members of an amino acid
transporter family.4 There is also good evidence that CD98
is functionally associated with The most striking feature of CD98 is the extraordinary diversity of
functions in which it has been implicated.7 Antibodies against CD98 block the formation of cell syncitia by human
immunodeficiency virus and other viruses,8,9 and CD98 also
appear to play a more general role in regulation of integrin-mediated
cell adhesion.6,10,11 CD98 has been implicated in
hematopoietic cell differentiation, growth, transformation, and
apoptosis,1,12 and recently this role has been extended to
the regulation of osteoblast differentiation.13 CD98 also
plays a role in the regulation of amino acid transport by virtue of its
associated light chain, as discussed above. Most recently, the molecule
has been implicated in the regulation of both antigen-presenting cell
function and T-cell activation.14,15 Our group's interest
in CD98 arose because we described its presence at very high levels on
the surface of human dendritic cells.16 Subsequently, we
showed that some antibodies to this molecule could block the ability of
both the U937 promonocyte line17 and human peripheral
blood-derived dendritic cells18 to deliver essential
costimulatory signals to T cells.
One central question in the biology of CD98 has been how to
understand the nature of its functional interactions with integrins and
other adhesion molecules at the cell surface. In this study, we have
developed and used a new quantitative assay of homotypic aggregation of
U937 cells, and we have re-examined this question in detail. Our
results confirm that there is an important interaction between CD98 and
CD29 ( Materials
The following antibodies were used in this study: CD18
(CLB-LFA1, immunoglobulin [Ig]-G1, ascites, CLB); CD18
(BU86, IgG1, ascites, kindly provided by D. Hardie, Birmingham
University, Birmingham, United Kingdom); CD29 (MEM
101A, IgG1, ascites, kindly provided by V. Horejsi); CD29
(P5D5, IgG1, purified antibody, gift from N. Hogg, Imperial Cancer
Research Fund (ICRF), London, United Kingdom); CD29 (MAR4, IgG1,
ascites, kindly provided by S. Menard, National Cancer Institute,
Milan, Italy); CD43 (161-46, ascites, IgG1, kindly provided by R. Villela, Centre of Immunology, Barcelona, Spain); CD44 (E1/2, IgG1,
purified antibody, Leinco Technologies, St Louis, MO); CD98 (BK19.9,
IgG1, purified antibody, kindly provided by A. van Agthoven,
Immunotech, Marseille, France); CD98 (4F2, IgG2a, ascites, kindly
provided by D. Fox); CD98 (BU53, IgG2a, purified antibody, kindly
provided by D. Hardie); CD98 (BU89, IgG1, purified antibody, kindly
provided by D. Hardie); CD98 (AHN-18.1 and AHN-18, IgG1 culture
supernatants, kindly provided by K. Skubitz); CD98 (MEM 108, IgG1,
ascites, kindly provided by V. Horejsi); CD147 (MEM M6/1, IgG1,
ascites, kindly provided by V. Horejsi); CD147 (H84HF, IgG2b, ascites,
kindly provided by K. Sagawa). The specificity of all the CD98 and
CD147 antibodies was confirmed on appropriately transfected cell
lines.19
F(ab)2 and Fab fragments of CD98 AHN-18 were
prepared by digestion of purified antibodies with pepsin and papain
according to standard methods. Fragments were purified by affinity
chromatography on protein A and analyzed by polyacrylamide gel electrophoresis.
Cell culture
Quantitative homotypic cell aggregation assay We placed 20 µL cells in RPMI 1640 medium supplemented with 10% FCS at 106 cells/mL in round-bottom wells of a 96-microwell plate. An equal volume of medium, with or without appropriate antibody, was added, and the cells were incubated at 37°C for 4 to 7 hours. The cells were resuspended gently, so as not to break up the clusters, and the number of unaggregated and total cells were counted in a hemocytometer. The percentage of cells in aggregates was determined by the following equation: % of cells in aggregates = [(total cells free cells)/total cells] × 100. All
values, expressed as mean ± SEM, were obtained from 3 to 6 replicate cultures, and the Student t test for unpaired observation between control and experimental samples was carried out
for statistical evaluation of a difference. Each individual experiment
was repeated a minimum of 3 times.
Cytofluorometric analysis Expression of CD98 on the surface of U937 cells was determined by flow cytometry. Cells (105) were washed with phosphate-buffered saline (PBS) staining buffer (containing 2% FBS and 1% sodium azide) and incubated in 50 µL staining buffer containing 10% rabbit serum for 10 minutes on ice and then with the primary antibody for a further 45 minutes. After washing 3 times with staining buffer, cells were treated with 1/20 dilution of fluorescein isothiocyanate (FITC)-conjugated rabbit anti-mouse IgG secondary antibody (Dako, Dakopatts, High Wycombe, United Kingdom). Cells were then washed 3 times with staining buffer and analyzed on a FACScan (Becton Dickinson, San Jose, CA). Expression of CD29, CD18, CD45, and HLA-DR was analyzed by direct binding of fluoresceinated antibodies by means of flow cytometry as above. FITC-conjugated anti-CD18 and anti-HLA-DR, and tetrahoclamine isothiocyanate-conjugated anti-CD29, were obtained from Immunotech (Marseilles, France) and Coulter Electronics (Bedfordshire, United Kingdom), respectively. FITC-conjugated-mouse anti-human CD45 was obtained from Serotec (Oxford, United Kingdom).MTT assay (colorimetric assay) for measurement of cell viability Cell viability was measured by standard MTT assay. We added 10 µL MTT solution (10 mg/mL in PBS) to each well of U937 cultures for 3 hours before the end of the culture period. The cells were lysed by the addition of 15% sodium dodecyl sulfate (SDS) for solubilization of formazan and the optical density (OD) at 570 nm (OD570-630) was measured by means of a Spectramax 250 microplate reader (Molecular Devices, Sunnyvale, CA).Phosphotyrosine analysis Cells (5 × 106 cells/mL) were washed 3 times in cold PBS containing 1 mM sodium orthovanadate and lysed in lysis buffer (20 mM Tris-HCl, pH 7.4, 2 mM EDTA, 2 mM ethyleneglycotetraacetic acid, 50 mM -glycerophosphate, 1 mM sodium orthovanadate, 1 mM dithiothreitol, 1% Triton X-100, 10%
glycerol, 10 µg/mL leupeptin, 10 µg/mL aprotinin, 10 µg/mL
pepstatin, 1 mM benzimide, and 2 mM hydrogen peroxide) for 30 minutes
with rotation at 4°C. The lysates were clarified by centrifugation at
16 000g for 10 minutes at 4°C, and stored at 20°C
until needed.
Cell lysates were then analyzed by immunoblotting. Proteins were separated on 10% SDS-polyacrylamide gels, and transferred by electroblotting to polyvinylidenedifluoride (PVDF) membrane. Membranes were blocked for 60 minutes in Tris-buffered saline containing 3% bovine serum albumin, 20 mM NaF, 2 mM EDTA, and 0.2% Tween 20 at room temperature. The membrane was incubated in antiphosphotyrosine antibody (mouse monoclonal IgG2b) (Upstate Biotechology, Lake Placid, NY) solution overnight at 4°C, washed 3 times with the same buffer, incubated for 45 minutes at room temperature in horseradish peroxidase-conjugated rabbit antimouse immunoglobulin, and then washed 3 times. Peroxidase activity was visualized by chemiluminescence detection (electrogenerated chemiluminescence reagents) (Amersham, Little Chalfont, Buckinghamshire, United Kingdom). Intensity of bands on film was quantified with Synpotic (Cambridge, United Kingdom) image analysis system and software.
Aggregation-inducing activity of CD98 antibodies is heterogeneous and is not correlated with binding activity The binding of a panel of 7 antibodies specific for CD98 to U937 cells is shown in Figure 1A. All the antibodies showed a unimodal binding profile by flow cytometry, and the level of binding was dependent on antibody concentration. The antibodies were then tested for their ability to induce homotypic aggregation of U937 cells (Figure 1B, ii-v, and Table 1). The antibody CD98-AHN-18 was the most potent inducer of aggregation; several others induced weaker aggregation (BK19.9, BU53, 4F2), while some antibodies did not induce any aggregation. An antibody known to activate signaling and homotypic aggregation through the CD291-integrin chain (MEM 101A) and an
antibody to CD43 (161-46) that is believed to induce aggregation via a
1-integrin-independent pathway20 were also tested in
the aggregation assay. Both these antibodies did induce aggregation of
the U937 cells (Figure 1B, vi-vii), although the morphology of the
clusters was different from that induced by CD98-AHN-18, as the
clusters tended to be tighter and more compact. Aggregation was not
induced simply by the presence of antibody on the surface of U937,
since antibodies to CD44, another molecule present on the surface of
U937,21 did not induce aggregation (Figure 1B,
viii).
The ability of the panel of CD98 antibodies to induce aggregation did not correlate with the level of binding to the U937 cell surface. To confirm this further, flow cytometry at a range of antibody concentrations was used to select a titer that gave a mean fluorescent channel number (MFI) of between 100 and 200. Aggregation at this titer was then measured with the quantitative assay. As shown in Table 1, aggregating activity is clearly independent of binding activity, and aggregation levels vary widely even when the concentrations of antibody used were chosen to give comparable levels of binding to the U937 cells. The characteristics of CD98-AHN-18-induced aggregation, as well as
binding, were examined in more detail (Figure
2). Binding increased in a linear fashion
for 6 hours and then reached a plateau. In contrast, aggregation
induced via CD29 (MEM 101A) or CD43 (161-46) was much more rapid
(Figure 2A). The quantitative level of CD98-AHN-18-induced aggregation
was dose dependent, but was maximal at subsaturating doses of bound
antibody. Further increase in antibody concentration above this optimal
level resulted in a lesser degree of aggregation (Figure 2B).
F(ab)2 fractions of CD98-AHN-18 also induced aggregation (Figure 2B). The presence of high levels of human or rabbit
immunoglobulin did not inhibit clustering (data not shown). In
contrast, Fab fragments of CD98 failed to induce any clustering.
CD98-induced aggregation does not lead to cell death Since a previous study1 had suggested that CD98 triggering could induce cell death, we tested whether the CD98 monoclonal antibody (mAb) AHN-18 also caused killing of U937. As shown in Figure 3, CD98-AHN-18 did not decrease MTT reduction at 48 hours (Figure 3A). Furthermore, CD98-AHN-18 did not appear to cause growth arrest of the U937 cells, since cell numbers during 48 hours in culture increased to the same amount in both treated and control groups (Figure 3B).
CD98-induced aggregation, but not CD29-induced aggregation, is resistant to EDTA but sensitive to deoxyglucose Since CD98 has been reported to associate with CD29 (1
integrin) in the cell surface,6 we compared the ability of
a number of inhibitors of cell function to block the aggregation
induced by antibodies to these 2 molecules, as well as aggregation
induced by CD43. As shown in Figure 4A,
aggregation by antibodies to CD29 and CD98 share the properties of
being sensitive to colchicine, cytochalasin, and low temperature, but
insensitive to cycloheximide. EDTA blocks the ability of the activating
1-integrin antibody (MEM 101A) to induce aggregation; however,
aggregation induced by the CD98 mAb AHN-18 is insensitive to the
presence of EDTA. Aggregation induced by CD43 antibody, in contrast,
was sensitive only to low temperature, suggesting a completely
different mechanism of action for this molecule.
CD98-dependent aggregation was also much more sensitive than CD29- or CD43-dependent aggregation to inhibition by the metabolic inhibitor deoxyglucose (Figure 4A). However, sensitivity to deoxyglucose was lost soon after addition of aggregating antibody (Figure 4B), suggesting that adenosine 5'-triphosphate dependence was an early step in the CD98-induced signaling pathway. CD98-induced aggregation and CD29-induced aggregation are associated with distinct patterns of tyrosine phosphorylation Previous studies have identified tyrosine phosphorylation as a downstream event in signaling by both1 integrins22 and CD98.23 As shown in Figure
5, a comparison of the pattern of phosphotyrosine proteins induced following activation of the U937 cells
with CD98-AHN-18 is similar to, but distinct from, that induced by the
activating CD29 antibody MEM 101A. In particular, CD98-AHN-18, but not
MEM 101A, induces a rapid strong phosphorylation of a 72-kd band. Both
antibodies induced bands at 114 and 155 kd.
Reciprocal cross-inhibition by antibodies to CD98 and CD29 In order to probe further the interaction between CD29 and CD98 in the induction of U937 aggregation, the abilities of blocking antibodies to each of these 2 molecules to inhibit aggregation induced by the other was tested. As shown in Figure 6A, 2 nonaggregating CD98 antibodies, MEM 108 and BU89, strongly inhibited CD98-AHN-18-induced aggregation. At the same concentration, CD98-MEM 108 showed no inhibition of aggregation induced by CD29 agonist antibody MEM 101A, while CD98-BU89 showed a significant but partial inhibition (panel B). In the reciprocal experiment, 2 inhibitory antibodies to CD29, P5D2 and MAR4, showed strong inhibition of CD29-induced (MEM 101A) aggregation (Figure 6E). P5D2, which almost totally blocked the agonist action of CD29-MEM 101A, and is known to block binding of1-integrin dimers
to fibronectin,6,24 did not have any inhibitory activity
against CD98-AHN-18-induced aggregation and indeed reproducibly
enhanced the aggregation observed (panel D). The other CD29-blocking
antibody, MAR4 (which does not block binding of 1-integrins to
fibronectin25), showed a small but reproducible inhibition
of CD98-AHN-18-induced aggregation (panel D). None of the blocking
antibodies to either CD98 or CD29 that were tested had any inhibitory
effect on CD43-induced aggregation (Figure 6C,F).
Inhibition of CD98-induced homotypic aggregation by antibodies to
2 as well as 1 integrins in
mediating CD98-induced adhesion. As predicted, blocking antibodies to
CD18, the 2-integrin chain, partially blocked aggregation induced
via CD98 (Figure 7A, top panel), but not
via CD29 (middle panel A) or via CD43 (bottom panel). Both antibodies,
at the same concentrations, showed strong inhibition of aggregation
induced by PMA (not shown). A panel of anti-intercellular adhesion
molecule (ICAM) 1, 2, and 3 (CD54, CD102, CD50) antibodies were also
tested, but none inhibited aggregation induced by CD98 (not
shown).
U937 cells express relatively little Inhibition of CD98-induced homotypic aggregation by antibodies to CD147 Since inhibition by integrin antibodies was only partial, we tested other antibodies previously shown to be expressed on U937 cells17 for the ability to block CD98-induced aggregation. Unexpectedly, the only significant inhibition was by 2 antibodies to CD147 (Figure 8A, left panel, and Figure 8B). The CD147 antibodies also significantly inhibited aggregation induced via CD29 (Figure 8A, middle panel). Neither CD147 antibody inhibited aggregation induced via CD43 (Figure 8A, left panel). Addition of CD147 antibody together with CD18 antibody, CD29 antibody, or all 3 together did not result in further inhibition greater than the level observed with the independent use of each antibody (not shown).
To establish whether CD147 was involved in the induction (signaling)
phase of CD98-induced aggregation, the influence of CD147 antibodies on
CD98-AHN-18-induced tyrosine phosphorylation was examined (Figure
9). The presence of CD147 antibody, as
well as the blocking CD98 antibody BU89, almost completely blocked
phosphorylation of the 72- and 155-kd band induced by CD98-AHN-18
ligation (lanes 3 and 5). Phosphorylation of the band(s) at around 114 kd was less strongly inhibited. CD147 also partially inhibited
CD29-induced tyrosine phosphorylation (lanes 4 and 6). CD147 ligation
alone did not induce any changes in protein tyrosine phosphorylation (Figure 9, lane 2). CD147 antibodies did not alter the level of CD98
expression when added 4, 9, or 24 hours before staining (data not shown).
Finally, to try to distinguish further between induction and effector
(cell-cell binding) phases of the CD98-AHN-18-induced homotypic
aggregation, we tested the ability of the various antibodies to block
aggregation when added either prior to, simultaneously with, or after
addition of the agonist antibody CD98-AHN-18 (Figure 10). CD29 antibody MAR4 blocked
CD98-AHN-18-induced aggregation when added 1.5 hours before addition
of CD98-AHN-18, but not when added simultaneously or 1.5 hours
afterwards. In contrast, antibodies to CD98 itself, to CD18, and to
CD147 inhibited to the same extent whether added before CD98-AHN-18 or
up to 1.5 hours afterwards.
The diversity of responses in which the 85-kd type II membrane protein, CD98, has been implicated supports the notion that the molecule probably plays a key role in cell-cell interaction and signaling, but (perhaps because of CD98 diversity and ubiquity) this role remains poorly understood. Our recent studies identified CD98 as a major component of the human dendritic cell surface16 and confirmed earlier reports15 that it is involved in T-cell costimulation.17,18 During the course of these studies, however, we also confirmed previous reports10 that some CD98 antibodies induced homotypic aggregation of the U937 cell line, and we focused on this model system to dissect the molecular basis of CD98 function, because of the advantages of working with a uniform cell line rather than a mixed population of T cells and antigen-presenting cells. A reproducible quantitative assay of U937 homotypic aggregation was
developed as a prelude to pharmacological and molecular dissection of
CD98 function, and the results from this assay form the basis for the
present study. It was clear from this assay that CD98 antibodies are
highly heterogenous both in function and in the ability to bind to CD98
on the U937 cell surface (Figure 1). It seems unlikely that this
heterogeneity simply reflects concentration or affinity of the
antibodies used, since each antibody was tested over a wide range of
concentrations. The heterogeneity is very reminiscent of aggregation
induced by anti- The next question we addressed, using the same assay, was the
relationship between CD98 and other cell-surface molecules thought to
have a role in cell-cell interaction. The functional association between CD98 and CD29 ( Several features of the CD29/CD98 results presented in this paper
suggest that CD29 molecules play a role in the inductive phase of the
response, rather than mediating the actual cell-cell adhesion. First,
the CD29 antibody that inhibited aggregation induced via CD98 is not
the same as the one that blocks the ability of In contrast, antibodies to The blocking of CD98-induced aggregation by CD147 was an unexpected
finding. CD147 is a member of the immunoglobulin superfamily, originally believed to be involved in blood-brain barrier
function.28 However, CD147 knockouts did not reveal any
defect in this function, but showed some behavioral and immunological
abnormalities.29 The ligand (if such a molecule exists)
for CD147 has not been described, and hence the partner for its role in
mediating cellular aggregation remains unknown. Most intriguingly,
however, recent reports have identified some striking parallels between
CD147 and CD98. CD147 associates physically with In CD98-mediated U937 aggregation, it is unclear whether CD147 is acting as an ancillary adhesion molecule or mediates the aggregation event itself. The inhibitory action of CD147 is manifest even when antibody is added 1.5 hours after CD98-AHN-18, consistent with a possible role for CD147 in mediating the cell-cell binding. However, an alternative hypothesis for these data is that continuous signaling via CD98 is required to produce aggregation and that CD147 interferes with this signaling event or even sends negative signals that oppose CD98-induced changes. This model is consistent with the observation that CD147 ligation profoundly inhibits the tyrosine phosphorylation induced by CD98-AHN-18 ligation. The data presented above, taken together with previous data on this
pleiotropic molecule, suggest that CD98 is a central component within a
multimolecular complex that can regulate outcomes as diverse as
adhesion, growth, differentiation, and antigen presentation. These data
prompt us to suggest a speculative model that links CD98-induced
aggregation, the central role of
Submitted September 14, 2000; accepted February 27, 2001.
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: Benjamin Chain, Department of Immunology, Windeyer Institute of Medical Sciences, UCL, 46 Cleveland St, London W1T 6JF, United Kingdom; e-mail: b.chain{at}ucl.ac.uk.
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© 2001 by The American Society of Hematology.
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 K. S. Vetrivel, X. Zhang, X. Meckler, H. Cheng, S. Lee, P. Gong, K. O. Lopes, Y. Chen, N. Iwata, K.-J. Yin, et al. Evidence That CD147 Modulation of {beta}-Amyloid (A{beta}) Levels Is Mediated by Extracellular Degradation of Secreted A{beta} J. Biol. Chem., July 11, 2008; 283(28): 19489 - 19498. [Abstract] [Full Text] [PDF]
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 S. M. Gallagher, J. J. Castorino, D. Wang, and N. J. Philp Monocarboxylate Transporter 4 Regulates Maturation and Trafficking of CD147 to the Plasma Membrane in the Metastatic Breast Cancer Cell Line MDA-MB-231 Cancer Res., May 1, 2007; 67(9): 4182 - 4189. [Abstract] [Full Text] [PDF]
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 S. T. Fraser, J. Isern, and M. H. Baron Maturation and enucleation of primitive erythroblasts during mouse embryogenesis is accompanied by changes in cell-surface antigen expression Blood, January 1, 2007; 109(1): 343 - 352. [Abstract] [Full Text] [PDF]
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 N. Intasai, S. Mai, W. Kasinrerk, and C. Tayapiwatana Binding of multivalent CD147 phage induces apoptosis of U937 cells Int. Immunol., July 1, 2006; 18(7): 1159 - 1169. [Abstract] [Full Text] [PDF]
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 P. Mina-Osorio, L. H. Shapiro, and E. Ortega CD13 in cell adhesion: aminopeptidase N (CD13) mediates homotypic aggregation of monocytic cells J. Leukoc. Biol., April 1, 2006; 79(4): 719 - 730. [Abstract] [Full Text] [PDF]
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 D. Xu and M. E. Hemler Metabolic Activation-related CD147-CD98 Complex Mol. Cell. Proteomics, August 1, 2005; 4(8): 1061 - 1071. [Abstract] [Full Text] [PDF]
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 N. J. Philp, J. D. Ochrietor, C. Rudoy, T. Muramatsu, and P. J. Linser Loss of MCT1, MCT3, and MCT4 Expression in the Retinal Pigment Epithelium and Neural Retina of the 5A11/Basigin-Null Mouse Invest. Ophthalmol. Vis. Sci., March 1, 2003; 44(3): 1305 - 1311. [Abstract] [Full Text] [PDF]
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 R. C. Rintoul, R. C. Buttery, A. C Mackinnon, W. S. Wong, D. Mosher, C. Haslett, and T. Sethi Cross-Linking CD98 Promotes Integrin-like Signaling and Anchorage-independent Growth Mol. Biol. Cell, August 1, 2002; 13(8): 2841 - 2852. [Abstract] [Full Text] [PDF]
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 T. C. Major, L. Liang, X. Lu, W. Rosebury, and T. M.A. Bocan Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) Is Induced Upon Monocyte Differentiation and Is Expressed in Human Atheroma Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1200 - 1207. [Abstract] [Full Text] [PDF]
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 F. Allain, C. Vanpouille, M. Carpentier, M.-C. Slomianny, S. Durieux, and G. Spik Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix PNAS, February 20, 2002; (2002) 52284899. [Abstract] [Full Text] [PDF]
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F. Allain, C. Vanpouille, M. Carpentier, M.-C. Slomianny, S. Durieux, and G. Spik Interaction with glycosaminoglycans is required for cyclophilin B to trigger integrin-mediated adhesion of peripheral blood T lymphocytes to extracellular matrix PNAS, March 5, 2002; 99(5): 2714 - 2719. [Abstract] [Full Text] [PDF]
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1-integrins, and
CD147 in the induction of U937 homotypic aggregation
Top
Abstract
Introduction
), 0.3 for MEM 108 (CD98, 
), 1.25 for P5D2 (CD29, 
/