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Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 649-655
Acute Regulation of Glucose Transport After Activation of Human
Peripheral Blood Neutrophils by Phorbol Myristate Acetate,
fMLP, and Granulocyte-Macrophage Colony-Stimulating Factor
By
An S. Tan,
Nuzhat Ahmed, and
Michael V. Berridge
From the Malaghan Institute of Medical Research, Wellington School of
Medicine, Wellington South, New Zealand.
 |
ABSTRACT |
Activation of human peripheral blood neutrophils by pathogens or by
phorbol myristate acetate (PMA), fMLP, or myeloid growth factors
generates a respiratory burst in which superoxide production plays an
important role in killing invading microorganisms. Although the
increased energy demands of activated neutrophils would be expected to
be associated with increased glucose uptake and utilization, previous
studies have shown that PMA inhibits 2-deoxyglucose (2-DOG) uptake. In
this study, we show that PMA activation of neutrophils, isolated by
methods not involving hypotonic lysis, increases the rate of 2-DOG
uptake and results in a 1.6-fold to 2.1-fold increase in transporter
affinity for glucose without changing Vmax. Increased transporter affinity in response to PMA was also observed with 3-O-methyglucose, which is not phosphorylated, and inclusion of glucose
in the activation medium further increased respiratory burst activity.
Increased 2-DOG uptake and increased transporter affinity for glucose
were also observed with the peptide activator, fMLP, and with
granulocyte-macrophage colony-stimulating factor (GM-CSF). The protein
kinase C (PKC) inhibitor, calphostin C, and the tyrosine kinase
inhibitor, genistein, inhibited both PMA- and fMLP-stimulated 2-DOG
uptake. In contrast, genistein inhibited fMLP-induced superoxide
production, but had little effect on the PMA-induced response, while
staurosporine differentially inhibited PMA-induced superoxide
production. These results show that neutrophil activation involves
increased glucose transport and intrinsic activation of glucose
transporter molecules. Both tyrosine kinases and PKC are implicated in
the activation process.
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INTRODUCTION |
THE INFLAMMATION THAT is associated with
infection is characterized by recruitment of professional phagocytes
and secretory cells including neutrophils, eosinophils, mast cells, and
mononuclear cells to the affected area. Several interrelated defense
mechanisms are deployed that include the release of highly toxic
secretory granule components, activation of the respiratory burst, and
phagocytosis. Although the respiratory burst activity of human
peripheral blood neutrophils has been studied intensively,1
and many components of the membrane-bound respiratory burst oxidase
responsible for superoxide production identified,2
knowledge of the way that neutrophils use endogenous and exogenous
energy supplies to fuel the respiratory burst is poorly understood.
Increased superoxide production that is associated with phagocytosis
and phorbol myristate acetate (PMA) treatment of neutrophils involves
increased glucose-C-1 metabolism via the hexose monophosphate (HMP)
shunt.3-6 With neutrophils, uptake of 2-deoxyglucose
(2-DOG) and certain amino acids has been shown to be inhibited by PMA along with the uptake of radiolabelled bacteria,4 but with peritoneal macrophages and macrophage cell lines, superoxide production in response to PMA and colony-stimulating factor (CSF)-1
was dependent on glucose in the culture media.6,7 These
results suggest that neutrophils may use endogenous energy supplies to
facilitate the respiratory burst, whereas macrophages rely on
exogenously supplied energy. In the short-term, simple sugar phosphates
in neutrophils could provide the energy needed for respiratory burst activity, but in the longer term, stored glycogen is used.8
Transport of glucose across the plasma membrane is a passive process
involving a family of structurally related `facilitative' glucose
transporter molecules, which shift glucose down its concentration gradient without expending energy.9 These transporters are often expressed in a tissue or cell-specific manner, and in some cases,
their expression is regulated by extracellular signals such as hormones
and growth factors.10 In adipose and muscle cells in the
short-term, increased glucose transport in response to insulin occurs
by translocation of Glut-4 from an intracellular pool to the plasma
membrane.11,12 Glut-1 is also recruited to the plasma
membrane in response to insulin, although this occurs to a much lesser
extent than Glut-4. In addition to increased plasma membrane
expression, there is also evidence that the intrinsic activity of
Glut-1 and Glut-4 are modulated in response to
insulin.13-16
Regulation of glucose transport in systems not involving insulin is
poorly understood. Stress induced by a variety of reagents stimulates
glucose transport by translocating transporters from intracellular
sites to the plasma membrane17 or by increasing transporter
expression.18 On the other hand, changes in the intrinsic
activity of Glut-1 have been associated with glucose deprivation19 or cadmium treatment20 of 3T3L1
cells and azide treatment of rat liver clone 9 cells.21,22
In hematopoietic cells, we and others have shown that interleukin
(IL)-3 and other growth factors stimulate glucose transport in growth
factor-dependent cells by increasing the affinity of glucose
transporters for glucose without a change in transporter expression or
Vmax.23,24 In other studies, the malignant
phenotype and acutely transforming viruses and oncogenes have been
associated with increased transporter affinity for
glucose,25,26 while apoptosis induced in human Jurkat cells
by an antibody against CD95 dramatically reduced the affinity of Glut-1
for glucose.27
To further investigate a possible relationship between glucose uptake
and respiratory burst activation, human peripheral blood neutrophils
were purified using Polymorphprep and their activation by PMA and fMLP
studied. Contrary to previous reports,4,28 we show that
increased superoxide production in response to PMA is associated with
increased 2-DOG uptake. Furthermore, a 1.6-fold to 2.1-fold increase in
affinity of glucose transporters for glucose was observed, and
physiologic concentrations of glucose in the incubation medium doubled
superoxide production. Increased transporter affinity for glucose was
also observed with fMLP and with the myeloid growth factor,
granulocyte-macrophage colony-stimulating factor (GM-CSF). Both
tyrosine kinase activity and protein kinase C (PKC) were shown to be
involved in PMA and fMLP stimulation of 2-DOG uptake, although
differential effects of these inhibitors were observed on superoxide
production. These results show that neutrophil activation involves
acute regulation of glucose transporter function.
| |
MATERIALS AND METHODS |
Collection and preparation of neutrophils.
Human peripheral blood neutrophils were collected from venous blood of
healthy donors using EDTA as an anticoagulant. Blood was layered over
an equal volume of Polymorphprep (Nycomed Pharma, Oslo, Norway) and
centrifuged at 500g for 30 minutes at 20°C. The lower band
containing polymorphonuclear leukocytes was collected, washed twice
with phosphate-buffered saline (PBS), and resuspended at a
concentration of 107/mL. Purity and viability were greater
than 95%.
Materials.
Calphostin C was obtained from Kamiya Biomedical Company (Thousand
Oaks, CA) and 2-DOG from Fluka (Buchs, Switzerland). All other
chemicals and enzymes including PMA, fMLP, cytochrome c, catalase,
genistein, and staurosporine were from Sigma Chemical Company (St
Louis, MO). Superoxide dismutase (SOD) was from Boehringer Mannheim
(Mannheim, Germany). Recombinant human GM-CSF was obtained from Dr J.D.
Watson, Genesis Research and Development Corporation, Auckland and was
sourced from Immunex, Seattle, WA.
Superoxide production.
Superoxide production was determined by measuring SOD-inhibitable
reduction of ferricytochrome c to the ferrous form. Briefly, 1 to 1.5 × 106 cells were incubated in 1 mL PBS, pH 7.4 containing 40 µmol/L cytochrome c and 20 µg/mL catalase with or
without 20 µg/mL SOD. Samples were equilibrated for 5 minutes at
37°C and the reaction initiated by adding PMA (100 ng/mL), fMLP
(0.5 µmol/L), or GM-CSF (100 ng/mL). All incubations were performed
at 37°C for 10 minutes unless stated otherwise. Reactions were
stopped by placing the tubes on ice for 5 minutes, after which the
cells were removed by centrifugation at 10,000g for 1 minute. The absorbance of the supernatant containing reduced cytochrome
c was measured at 550 nm against a blank containing all reagents except
the cells. Superoxide production was calculated using a millimolar
extinction coefficient of 21.1.
[3H]-2-DOG uptake.
2-DOG uptake was measured by the zero-trans method using
[3H]-2-deoxy-D-glucose (2-DOG, 100 µmol/L, 1 µCi,
Amersham, UK) as described previously.24 Neutrophils
(106) were preincubated in 1 mL PBS for 5 minutes at
37°C before adding PMA, fMLP, or GM-CSF for the times indicated.
Cells were recovered by centrifugation and suspended in 0.25 mL PBS
containing [3H]-2-DOG. Uptake was stopped by adding
ice-cold PBS containing 0.3 mmol/L phloretin and cells collected by
microcentrifugation at 10,000g for 1 minute through a cushion
of 10% bovine serum albumin (BSA). The cell pellet was washed, lysed
in 0.1 mL 1% Triton X-100, and radioactivity determined. Kinetic
analysis of 2-DOG uptake used 0.1 to 4 mmol/L 2-DOG in the
extracellular medium and uptake was determined over 3 minutes. Where
inhibitors were used, cells were treated with the inhibitors for 20 minutes before addition of PMA, fMLP, or growth factor.
[3H]-3-O methylglucose uptake.
3-O-methylglucose uptake was measured by the zero-trans method
described above, using [3H]-3-O-methylglucose (3-O-MG,
100 µmol/L, 1 µCi, Amersham). Uptake was determined at 37°C in
50 µL glucose-free RPMI instead of PBS and was performed over 3 seconds, which approached the linear range of the uptake curve.
| |
RESULTS |
Effects of PMA on superoxide production and [3H]-2-DOG
uptake by neutrophils.
Human peripheral blood neutrophils were prepared by a one-step density
fractionation procedure using Polymorphprep. Neutrophils were washed
twice in PBS before stimulation with 100 ng/mL PMA for the times
indicated. This concentration of PMA had previously been shown to be
optimum for both superoxide production and for [3H]-2-DOG uptake. Figure 1A
shows that superoxide production, determined as SOD-inhibitable
cytochrome c reduction, increased linearly over 30 minutes. In
contrast, the rate of [3H]-2-DOG uptake, determined over
3-minute intervals at the times indicated, continued to increase over
60 minutes (Fig 1B). An approximate twofold increase in the rate of
[3H]-2-DOG uptake was observed at 60 minutes.
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| Fig 1.
Effect of PMA on superoxide production by neutrophils and
on [3H]-2-DOG uptake. (A) SOD-inhibitable cytochrome c
reduction. Neutrophils (106) were treated with 100 ng/mL
PMA for increasing times in the presence and absence of SOD. Control
absorbance (A550 + SOD) was 0.364 ± 0.009. (B)
[3H]-2-DOG uptake determined over 3-minute intervals at
the times indicated after exposure to PMA. Each value represents the
mean of duplicate determinations obtained from two separate
experiments. [3H]-2-DOG uptake at zero time was 1619 ± 41 cpm.
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Effects of PMA on the kinetics of 2-DOG uptake by neutrophils.
To determine whether the increased 2-DOG uptake observed after
activation of neutrophils with PMA was associated with changes in
transport kinetics, cells were treated with or without 100 ng/mL PMA
for 10 minutes or 30 minutes before determining
[3H]-2-DOG uptake over 3-minute intervals using a range
of 2-DOG concentrations (0.1 to 4 mmol/L). Lineweaver-Burk analysis of the results of several experiments is summarized in
Table 1. At both time points, PMA treatment
significantly reduced transporter Km for glucose without
affecting Vmax. Other methods of analysis, eg,
Eadie-Hofstee plots gave similar results. The possibility that
posttransport phosphorylation of 2-DOG may influence uptake kinetics
was explored using the nonphosphorylatable glucose analogue 3-O-methylglucose. With this sugar, an uptake time of 3 seconds was
used, as this was as close as we could get to the linear range of the
uptake curve without compromising reproducibility. With 3-O-MG, PMA
treatment for 10 minutes increased the affinity of glucose transporters
for glucose by 21% without changing Vmax. Thus,
neutrophils treated with PMA for 10 minutes exhibited a Km
(mmol/L) of 2.79 ± 0.12 compared with 3.54 ± 0.04 for untreated controls (n = 2), whereas Vmax
(nmol/106cells/minute) was 10.1 ± 0.1 and 10.37 ± 0.27, respectively.
Superoxide production by neutrophils is facilitated by exogenous
glucose.
The effects of PMA on 2-DOG uptake by neutrophils described above were
determined in PBS without added glucose. The possibility that glucose
may promote PMA-stimulated superoxide production was therefore
determined. Figure 2 shows that
PMA-stimulated superoxide production increased with the concentration
of D-glucose to a plateau 2.5-fold at 5 to 10 mmol/L glucose. Thus, at
physiologic concentrations of glucose, near maximum effects of PMA on
superoxide production were observed. Figure 2 also shows the effects of
glucose on superoxide production in the presence of
divalent cations. Although the response curve was shifted, the
fractional effect on 2-DOG uptake remained similar to that in the
absence of Ca2+/Mg2+.
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| Fig 2.
Effect of D-glucose on superoxide production by human
neutrophils. Neutrophils (106) were treated with 100 ng/mL
PMA in the presence of increasing concentrations of D-glucose for 20 minutes at 37°C and SOD-inhibitable cytochrome c reduction
determined. Result are the average of two experiments involving
duplicate determinations made in the presence ( ) or absence ( ) of
1.4 mmol/L Ca2+ and Mg2+. Control
absorbances at A550 (no glucose) were 0.722 ± 0.19 and 0.605 ± 0.017, respectively and in the presence of SOD, 0.376 ± 0.007 and 0.364 ± 0.013, respectively.
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Effects of fMLP and the myeloid growth factor, GM-CSF on
[3H]-2-DOG uptake by neutrophils.
Figure 3 compares the effects of fMLP on
superoxide production and [3H]-2-DOG uptake by
neutrophils. Maximum effects of fMLP were observed within 4 to 8 minutes at 10-7 to 10-8 M fMLP. Interestingly,
[3H]-2-DOG uptake showed slightly greater sensitivity to
fMLP than did superoxide production (Fig 3A and C). Increased 2-DOG
uptake was also observed after treatment with GM-CSF for 60 minutes. At
optimum times of stimulation by fMLP and GM-CSF, increased 2-DOG uptake
was associated with a 4.5-fold to fivefold increase in transporter
affinity for glucose, but with these activators, some reduction in
Vmax was also observed (Table 1). With GM-CSF, only a small
(30%) increase in superoxide production was observed consistent with
its role in neutrophil priming (compared with 1.6-fold to
threefold increase with PMA and fMLP).
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| Fig 3.
Effect of fMLP on superoxide production and
[3H]-2-DOG uptake by human neutrophils. Neutrophils
(106) were incubated with 0.5 µmol/L fMLP for the times
indicated (B and D) or for 5 minutes at the concentrations indicated (A and C) and SOD-inhibitable cytochrome c reduction (A and B) and [3H]-2-DOG uptake (C and D) determined. The results are
the average of duplicate determinations. For (A) and (B), control
absorbances (A550) in the presence of SOD were 0.342 ± 0.003 and 0.305 ± 0.003, respectively, and for (C) and (D), control
uptake was 2,613 ± 32 cpm and 2,068 ± 94 cpm, respectively.
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Effects of protein kinase inhibitors on PMA and fMLP stimulation of
[3H]-2-DOG uptake and superoxide production.
The PKC inhibitor, calphostin C, and the tyrosine kinase inhibitor,
genistein, inhibited 2-DOG uptake stimulated by PMA and fMLP by 60% to
70%, and this was similar to the level of inhibition observed in the
absence of the activating molecules (Fig
4). These results contrast with the effects of PKC and tyrosine kinase
inhibitors on superoxide production stimulated by PMA and fMLP
(Fig 5). Genistein extensively inhibited
fMLP-stimulated superoxide production, but had little effect on the
PMA-induced response (Fig 5B). In contrast, PMA-stimulated superoxide
production showed fourfold greater sensitivity to the protein kinase
inhibitor, staurosporine, than the fMLP response (Fig 5A).
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| Fig 4.
Effects of genistein and calphostin C on
[3H]-2-DOG uptake by unstimulated and stimulated human
neutrophils. Neutrophils (106) were pretreated without
(solid bars) or with 100 µmol/L genistein (patterned bars) or 1 µmol/l calphostin C (shaded bars) for 20 minutes before stimulation
with 100 ng/mL PMA for 20 minutes or 0.5 µmol/L fMLP for 5 minutes
and [3H]-2-DOG uptake determined over 3 minutes in the
absence of inhibitor. Results are the average of duplicate
determinations.
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| Fig 5.
Effects of genistein and staurosporine on PMA and fMLP
stimulation of human neutrophils. (A) Neutrophils (106)
were pretreated without or with increasing concentrations of staurosporine for 20 minutes before stimulation with 100 ng/mL PMA for
20 minutes () or 0.5 µmol/L fMLP for 5 minutes () and determination of SOD-inhibitable cytochrome c reduction. (B)
Neutrophils (106) were pretreated with or without 100 µmol/L genistein before stimulation with 100 ng/mL PMA for 20 minutes
or 5 × 10-7 mol/L fMLP for 5 minutes and determination of
SOD-inhibitable cytochrome c reduction. Results are the average of
duplicate determinations. Control absorbances were: (A) unstimulated
cells, 0.336 ± 0.013; PMA-treated, 0.931 ± 0.005; fMLP-treated,
0.754 ± 0.008. (B) Unstimulated cells, 0.386 ± 0.005; PMA-treated,
0.606 ± 0.015; fMLP-treated 0.540 ± 0.007.
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DISCUSSION |
The phagocytic respiratory burst of human peripheral blood neutrophils
can be activated by the phorbol ester, PMA, by the peptide, fMLP, and
to a lesser extent by the myeloid growth factor, GM-CSF. In this study,
we show coordinate stimulation of superoxide production and glucose
uptake by neutrophils after activation by PMA and fMLP. With GM-CSF,
enhanced 2-DOG uptake was associated with a relatively small increase
in superoxide production. Thus, previous reports that PMA inhibits
2-DOG uptake by neutrophils4,28 were not substantiated.
Rather, activated neutrophils showed enhanced glucose transporter
activity and were able to use extracellular glucose, as well as
intracelluar energy supplies, to fuel the respiratory burst. The reason
why we have been able to show that the respiratory burst and glucose
uptake are coordinately regulated most likely relates to the gentle
one-step procedure currently used to isolate neutrophils. In the
earlier studies, density separation was followed by hypotonic lysis in
deionized or distilled water to remove residual erythrocytes.
Comparison of respiratory burst activation of these neutrophils with
those prepared by the Polymorphprep procedure used in the present
study, showed an approximate fivefold greater ability to produce
superoxide when hypotonic lysis was not used. Reduced
glucose transporter function in neutrophils subjected to hypotonic
lysis is indicated by lower Vmax values for 2-DOG uptake in
a study by Potashnik et al29 (0.51 ± 0.11 nmol/106 cells/minute) compared with 2.7 to 3.2 nmol/106 cells/minute in the present study. It is also
interesting to note that the Km values reported in the
study of Potashnik et al are those of PMA-activated neutrophils (Fig
3), explaining perhaps, the failure of De Chatelet et al4
to further increase 2-DOG uptake after PMA activation. A more recent
study of the effect of fMLP on hexose transport in polymorphonuclear
leukocytes30 showed a twofold to fivefold increase in 2-DOG
and 3-O-MG transport in response to fMLP, while another brief
report31 indicated increased transport in response to PMA,
contradicting previous reports.4,28
Increased 2-DOG uptake by human peripheral blood neutrophils after
treatment with PMA was associated with functional activation of glucose
transporter molecules on the cell surface. Thus, a twofold increase in
glucose transporter affinity for glucose was observed at both 10 minutes and 30 minutes after PMA activation without a significant
change in Vmax. However, the increasing rate of 2-DOG
uptake shown in Fig 1B cannot be fully explained in terms of
transporter affinity changes alone, as the increased affinity remained
unchanged between 10 minutes and 30 minutes, during which time the rate
of 2-DOG uptake increased by about 25%. Attempts to analyze the
kinetics of 2-DOG uptake after 60 minutes treatment with PMA failed to
show any further increase in transporter affinity for 2-DOG (results
not shown). Therefore, it appears that additional mechanisms need to be
invoked to explain the increased rate of 2-DOG uptake in response to
PMA at times greater than 10 minutes. Although a possible contribution
of 2-DOG phosphorylation to the observed kinetic changes cannot be
ruled out, transporter activation was also observed when the
nonphosphorylatable hexose, 3-O-MG, was used adding support to the
activation model. Our results differ from those obtained with the
chemotactic peptide, fMLP, where a fivefold increase in
Vmax was observed without a change in Km, both
with 2-DOG and 3-O-MG.30
Increased 2-DOG uptake and intrinsic activation of glucose transporters
on neutrophils in response to PMA was initially demonstrated in PBS.
However, addition of D-glucose increased PMA-induced superoxide production 2.5-fold, showing that increased glucose transport and
transporter activation may be physiologically relevant. These results
suggest that acute activation of the respiratory burst is contributed
to about equally by extracellular glucose and intracellular energy
sources. In the longer term, neutrophil glycogen reserves would be
mobilized.8
The respiratory burst can also be activated in bone marrow and
peritoneal macrophages and macrophage cell lines in response to PMA and
myeloid growth factors,6,7,32 but in these situations, extracellular glucose is mandatory for respiratory burst activation and
for the associated increase in 2-DOG uptake. With rat peritoneal macrophages stimulated with CSF-1 or PMA, increased 2-DOG uptake was
associated with a 40% increase in transporter affinity for glucose,6,33 and this correlated with hexokinase
translocation to the plasma membrane and coupling to sugar transport.
Although Kiyotaki et al7 failed to detect a change in
transporter affinity after PMA stimulation of the murine macrophage
cell line, J774.16, we have consistently observed twofold to fourfold
increased affinity of Glut-3 for glucose in RAW 264.7 cells activated
by PMA, fMLP, and GM-CSF, and with IL-3 despite its inability to
promote superoxide production.34
Human peripheral blood neutrophils express the glucose transporter
subtype, Glut-1, no detectable Glut-3 being observed (N. Ahmed and M.V.
Berridge, unpublished results). Therefore, regulation of the glucose
transport activity of Glut-1 is implicated. Although the rapid
neutrophil responses and the kinetic parameters observed are
inconsistent with increased glucose transport being explained by an
increase in gene and protein expression, we cannot exclude the
possibility that transporter translocation from an internal pool may
contribute to the observed increase in transport. However, with PMA,
the fact that Vmax did not change significantly suggests that translocation contributes little to the changes in glucose transport described in this study.
Inhibitor studies showed that glucose uptake into unstimulated
neutrophils is dependent on both tyrosine kinase and PKC activity. Likewise PMA and fMLP-stimulated 2-DOG uptake was inhibited by genistein and calphostin C (Fig 4). These results contrast with the
effects of the inhibitors on superoxide production in that fMLP-stimulated superoxide production was differentially inhibited by
genistein, whereas PMA-stimulated superoxide production exhibited greater sensitivity to staurosporine. Differential effects of staurosporine on PMA-stimulated superoxide production by neutrophils have previously been noted,35,36 whereas genistein has been shown to differentially inhibit fMLP-induced respiratory burst activity.37
| |
FOOTNOTES |
Submitted May 5, 1997;
accepted September 10, 1997.
Supported by the Cancer Society of New Zealand and its Wellington
Division and by the Health Research Council of New Zealand.
Address reprint requests to Michael V. Berridge, PhD,
Malaghan Institute of Medical Research, PO Box 7060, Wellington South, New Zealand.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. section 1734 solely
to indicate this fact.
| |
ACKNOWLEDGMENT |
We thank Dr Jim Watson for providing GM-CSF, Dr Gwyn Gould for
providing the antisera against human Glut-3, and Maya Kansara for
initial analysis of glucose transporter expression.
| |
REFERENCES |
1.
Babior BM:
The respiratory burst of phagocytes.
J Clin Invest
73:599,
1984
2.
Chanock SJ,
El Benna J,
Smith RM,
Babior BM:
The respiratory burst oxidase.
J Biol Chem
269:24519,
1994[Free Full Text]
3.
Babior BM,
Kipnes RS,
Curnutte JT:
Biological defense mechanisms. The production by leukocytes of superoxide, a potential bacteriocidal agent.
J Clin Invest
52:741,
1973
4.
DeChatelet LR,
Shirley PS,
Johnston RB:
Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes.
Blood
47:545,
1976[Abstract/Free Full Text]
5.
Sbarra AJ,
Karnovsky ML:
The biochemical basis of phagocytosis. 1. Metabolic changes during the ingestion of particles by polymorphonuclear leukocytes.
J Biol Chem
234:1355,
1979
6.
Rist RJ,
Jones GE,
Naftalin RJ:
Effects of macrophage colony-stimulating factor and phorbol myristate acetate on 2-D-deoxyglucose transport and superoxide production in rat peritoneal macrophages.
Biochem J
278:119,
1991
7.
Kiyotaki C,
Peisach J,
Bloom BR:
Oxygen metabolism in cloned macrophage cell lines: glucose.
J Immunol
132:857,
1984[Abstract]
8. Klebanoff SJ, Clark RA: The Neutrophil: Function and Clinical
Disorders. Amsterdam, The Netherlands, North Holland, 1978, p
326
9.
Carruthers A:
Facilitated diffusion of glucose.
Physiol Rev
70:1135,
1990[Free Full Text]
10.
Merrall NW,
Plevin R,
Gould GW:
Growth factors, mitogens, oncogenes and the regulation of glucose transport.
Cell Signal
5:667,
1993[Medline]
[Order article via Infotrieve]
11.
Suzuki K,
Kono T:
Evidence that insulin causes translocation of glucose transport activity to the plasma membrane from an intracellular storage site.
Proc Natl Acad Sci USA
77:2542,
1980[Abstract/Free Full Text]
12.
Cushman SW,
Wardzala LJ:
Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane.
J Biol Chem
255:4758,
1980[Free Full Text]
13.
Whitesell RR,
Abumrad NA:
Increased affinity predominates in insulin stimulation of glucose transport in the adipocyte.
J Biol Chem
260:2894,
1985[Abstract/Free Full Text]
14.
Toyoda N,
Flanagan JE,
Kono T:
Reassessment of insulin effects on the Vmax and Km values of hexose transport in isolated rat epididymal adipocytes.
J Biol Chem
262:2737,
1987[Abstract/Free Full Text]
15.
Harrison SA,
Buxton JM,
Czech MP:
Suppressed intrinsic catalytic activity of GLUT1 glucose transporters in insulin-sensitive 3T3-L1 adipocytes.
Proc Natl Acad Sci USA
88:7839,
1991[Abstract/Free Full Text]
16.
Harrison SA,
Clancy BM,
Pessino A,
Czech MP:
Activation of cell surface glucose transporters measured by photoaffinity labeling of insulin-sensitive 3T3-L1 adipocytes.
J Biol Chem
267:3783,
1992[Abstract/Free Full Text]
17.
Pasternak CA,
Aiyathurai JE,
Makinde V,
Davies A,
Baldwin SA,
Konieczko EM,
Widnell CC:
Regulation of glucose uptake by stressed cells.
J Cell Physiol
149:324,
1991[Medline]
[Order article via Infotrieve]
18.
Bashan N,
Burdett E,
Hundal HS,
Klip A:
Regulation of glucose transport and GLUT1 glucose transporter expression by O2 in muscle cells in culture.
Am J Physiol
262:C682,
1992[Abstract/Free Full Text]
19.
Fisher MD,
Frost SC:
Translocation of Glut-1 does not account for elevated glucose transport in glucose-deprived 3T3-L1 adipocytes.
J Biol Chem
271:11806,
1996[Abstract/Free Full Text]
20.
Harrison SA,
Buxton JM,
Clancy BM,
Czech MP:
Evidence that erythroid-type glucose transporter intrinsic activity is modulated by cadmium treatment of mouse 3T3-L1 cells.
J Biol Chem
266:19438,
1991[Abstract/Free Full Text]
21.
Shetty M,
Loeb JN,
Vikstrom K,
Ismailbeigi F:
Rapid activation of GLUT-1 glucose transporter following inhibition of oxidative phosphorylation in clone-9 cells.
J Biol Chem
268:17225,
1993[Abstract/Free Full Text]
22.
Shi Y,
Liu H,
Vanderburg G,
Samuel SJ,
Ismail BF,
Jung CY:
Modulation of GLUT1 intrinsic activity in clone 9 cells by inhibition of oxidative phosphorylation.
J Biol Chem
270:21772,
1995[Abstract/Free Full Text]
23.
Nefesh I,
Bauskin AR,
Alkalay I,
Golembo M,
Ben-Neriah Y:
IL-3 facilitates lymphocyte hexose transport by enhancing the intrinsic activity of the transport system.
Int Immunol
3:827,
1991[Abstract/Free Full Text]
24.
Berridge MV,
Tan AS:
IL-3 facilitates glucose transport in a myeloid cell line by regulating the affinity of the glucose transporter for glucose: Involvement of protein phosphorylation in transporter activation.
Biochem J
305:843,
1995
25.
White MK,
Bramwell ME,
Harris H:
Kinetic parameters of hexose transport in hybrids between malignant and nonmalignant cells.
J Cell Sci
62:49,
1983[Abstract]
26.
Ahmed N,
Berridge MV:
Regulation of glucose transport by interleukin-3 in growth factor-dependent and oncogene-transformed bone marrow-derived cell lines.
Leuk Res
21:609,
1997[Medline]
[Order article via Infotrieve]
27.
Berridge MV,
Tan AS,
McCoy KD,
Kansara M,
Rudert F:
CD95 (Fas/Apo-1)-induced apoptosis results in loss of glucose tramsporter function.
J Immunol
156:4092,
1996[Abstract]
28.
DeChatelet LR,
Lees CJ,
Walsh CE,
Long GD,
Shirley PS:
Comparison of the calcium ionophore and phorbol myristate acetate on the initiation of the respiratory burst in human neutrophils.
Infect Immun
38:969,
1982[Abstract/Free Full Text]
29.
Potashnik R,
Moran A,
Moses SW,
Peleg N,
Bashan N:
Hexose uptake and transport in polymorphonuclear leukocytes from patients with glycogen storage disease Ib.
Pediatr Res
28:19,
1990[Medline]
[Order article via Infotrieve]
30.
Okuno Y,
Gliemann J:
Effect of chemotactic factors on hexose transport in polymorphonuclear leucocytes.
Biochim Biophys Acta
941:157,
1988[Medline]
[Order article via Infotrieve]
31.
McCall C,
Schmitt J,
Cousart S,
O'Flaherty J,
Bass D,
Wykle R:
Stimulation of hexose transport by polymorphonuclear leukocytes: A possible role for protein kinase C.
Biochem Biophys Res Commun
126:450,
1985[Medline]
[Order article via Infotrieve]
32.
Hamilton JA,
Vairo G,
Lingelbach SR:
Activation and proliferation signals in murine macrophages: Stimulation of glucose uptake by hemopoietic growth factors and other agents.
J Cell Physiol
134:405,
1988[Medline]
[Order article via Infotrieve]
33.
Pedley KC,
Jones GE,
Magnani M,
Rist RJ,
Naftalin RJ:
Direct observation of hexokinase translocation in stimulated macrophages.
Biochem J
291:515,
1993
34.
Ahmed N,
Kansara M,
Berridge MV:
Acute regulation of glucose transport in a monocyte-macrophage cell line: Glut-3 affinity for glucose is enhanced during the respiratory burst.
Biochem J
327:369,
1997
35.
Dewald B,
Thelen M,
Wymann MP,
Baggiolini M:
Staurosporine inhibits the respiratory burst and induces exocytosis in human neutrophils.
Biochem J
264:879,
1989[Medline]
[Order article via Infotrieve]
36.
Combadiere C,
El Benna J,
Pedruzzi E,
Hakim J,
Perianin A:
Stimulation of the human neutrophil respiratory burst by formyl peptides is primed by a protein kinase inhibitor, staurosporine.
Blood
82:2890,
1993[Abstract/Free Full Text]
37.
Dusi S,
Donini M,
Rossi F:
Tyrosine phosphorylation and activation of NADPH oxidase in human neutrophils: A possible role for MAP kinases and for a 75 kDa protein.
Biochem J
304:243,
1994
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Abstract
Introduction
Abstract