Glutamine utilisation by rat neutrophils

Curi, Tânia Cristina Pithon; Melo, Mariza Pires de; Azevedo, Ricardo Bentes; Curi, Rui

doi:10.1042/bst025249s

Cited by 25 publications

(18 citation statements)

References 4 publications

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“…Similar to lymphocytes and macrophages [6][7][8], neutrophils also utilize glucose and glutamine at high rates [9,10]. The role of high rates of utilization of these fuels has not been determined, but may be related to the requirement for glucose both for new membrane synthesis during active periods of phagocytosis and for production of NADPH (via the pentose phosphate pathway), which is subsequently consumed via NADPH oxidase, thus producing O − : # .…”

Section: Introductionmentioning

confidence: 99%

“…The role of high rates of utilization of these fuels has not been determined, but may be related to the requirement for glucose both for new membrane synthesis during active periods of phagocytosis and for production of NADPH (via the pentose phosphate pathway), which is subsequently consumed via NADPH oxidase, thus producing O − : # . Glutamine is metabolized in neutrophils, producing glutamate, aspartate, alanine and lactate [9,10]. However, the contribution of glutaminolysis to neutrophil function has not yet been addressed.…”

Section: Introductionmentioning

confidence: 99%

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Effects of adrenaline on glucose and glutamine metabolism and superoxide production by rat neutrophils

García¹,

PITHON-CURI²,

FIRMANO³

et al. 1999

Clinical Science

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Despite the large body of information on the role of corticosteroids in regulating lymphocyte and phagocyte function, the role of the hormone adrenaline in immunoregulation is an under-investigated topic. The present study has addressed the effects of adrenaline on the rates of utilization and oxidation of glucose and glutamine, the phagocytic capacity and the rate of superoxide production by rat neutrophils. Incubation of rat neutrophils in the presence of 50 microM adrenaline caused a marked elevation in glucose metabolism, an effect that could be blocked by propranolol. Adrenaline caused a partial inhibition of glutamine utilization by neutrophils, an effect that was also blocked by propranolol. These effects of adrenaline could be mimicked by 100 microM dibutyryl cAMP. Phosphate-dependent glutaminase activity was significantly elevated in neutrophils incubated in the presence of 50 microM adrenaline or 100 microM dibutyryl cAMP for 1 h, whereas glutamine oxidation was significantly depressed (P<0.05) under these conditions. The elevation in enzyme activity was only partially blocked by propranolol. The phagocytic activity of rat neutrophils was not altered by adrenaline in the presence of either glucose or glutamine. The rate of phorbol 12-myristate 13-acetate-induced superoxide production in the presence of glucose was potently reduced by the addition of 5 nM or 50 microM adrenaline. This effect could be mimicked by dibutyryl cAMP. However, when rat neutrophils were incubated in the presence of glutamine plus adrenaline (5 nM or 50 microM), the rate of superoxide production was only marginally reduced. These findings support the proposition that adrenaline may deviate the flux of glucose from the NADPH-producing pentose phosphate pathway, thus reducing substrate availability for the superoxide-generating NADPH oxidase. However, glutamine metabolism may still give rise to substantial quantities of NADPH from the glutaminolysis pathway. We postulate that glutamine metabolism may thus provide a protective mechanism against the inhibitory effect of adrenaline on superoxide production by neutrophils.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of adrenaline on glucose and glutamine metabolism and superoxide production by rat neutrophils

García¹,

PITHON-CURI²,

FIRMANO³

et al. 1999

Clinical Science

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“…Consistent with these findings, others have implicated PMN in the generation of glutamate. For instance, in a whole cell metabolic assay, Curi et al (32) demonstrate that rat PMNs can use glutamine to generate large amounts of intracellular glutamate and extracellular glutamate can inhibit glutamine utilization by PMNs (31,32). Although we do not presently know the mechanism(s) of glutamate release from PMNs, it is likely to occur through well characterized pathways such as glutamate transporter reversal (33).…”

Section: Glutamate and Mglur Agonists Alter In Vitro Endothelialmentioning

confidence: 99%

Neutrophil-derived Glutamate Regulates Vascular Endothelial Barrier Function

Collard¹,

Park²,

Montalto³

et al. 2002

Journal of Biological Chemistry

151

125

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Endothelial barrier function is altered by the release of soluble polymorphonuclear leukocyte (PMN)-derived mediators during inflammatory states. However, endogenous pathways to describe such changes are only recently appreciated. Using an in vitro endothelial paracellular permeability model, cell-free supernatants from formylmethionylleucylphenylalanine-stimulated PMNs were observed to significantly alter endothelial permeability. Biophysical and biochemical analysis of PMN supernatants identified PMN-derived glutamate in modulating endothelial permeability. Furthermore, novel expression of metabotropic glutamate receptor 1 (mGluR1), mGluR4, and mGluR5 by human brain and dermal microvascular endothelial cells was demonstrated by reverse transcription-PCR, in situ hybridization, immunofluorescence, and Western blot analysis. Treatment of human brain endothelia with glutamate or selective, mGluR group I or III agonists resulted in a time-dependent loss of phosphorylated vasodilatorstimulated phosphoprotein (VASP) and significantly increased endothelial permeability. Glutamate-induced decreases in brain endothelial barrier function and phosphorylated VASP were significantly attenuated by pretreatment of human brain endothelia with selective mGluR antagonists. These observations were extended to an in vivo hypoxic mouse model in which pretreatment with mGluR antagonists significantly decreased fluorescein isothiocyanate-dextran flux across the blood-brain barrier. We conclude that activated human PMNs release glutamate and that endothelial expression of group I or III mGluRs function to decrease human brain endothelial VASP phosphorylation and barrier function. These results identify a novel pathway by which PMN-derived glutamate may regulate human endothelial barrier function.

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“…Glutamine is an important respiratory fuel for the intestinal tract, rapidly reproducing cells, and some immune cells, and supplementing TPN with glutamine partially supports mucosal immunity. [16][17][18][19][20] Clinically, glutamine-supplemented parenteral nutrition affects outcome in adults receiving allogeneic bone marrow transplants for hematologic malignancies.21 It was intriguing that the patients receiving glutamine had a significantly lower incidence of positive microbial cultures of the throat and stools and fewer clinical infections. Because the mucosal immune system also influences colonization patterns an vivo, we hypothesized that GLN supplementation would normalize the intestine cytokine profiles and both intestinal and extraintestinal levels of IgA.…”

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confidence: 98%