Glucose, but not glutamine, protects against spontaneous and anti-Fas antibody-induced apoptosis in human neutrophils.
Neutrophils are phagocytic cells of the innate immune system that use a combination of reactive oxygen species and anti-microbial toxins to kill and destroy ingested micro-organisms. Once they have performed their function, neutrophils die by apoptosis, which is important for the effective resolution of the inflammatory response. Both glucose and glutamine are important fuels for neutrophils, yet little has been done to investigate the comparative effects of glucose and glutamine on neutrophil apoptosis. We hypothesized that glucose and/or glutamine significantly alter rates of spontaneous and anti-Fas antibody-induced apoptosis of human neutrophils cultured ex vivo. Neutrophil apoptosis was reduced by increasing the extracellular concentration of glucose, but was unaffected by glutamine concentration. The protective effect of glucose appeared to correlate with the rate of glucose utilization. The addition of a competitive inhibitor of glycolysis, 2-deoxy-D-glucose (10 mM), attenuated the protective effect of 5.5 mM glucose, indicating that glucose metabolism is essential for its protective effect against apoptosis. There was a significant (P<0.05) reduction in the intracellular ATP concentration of neutrophils incubated in the absence of extracellular glucose compared with cells incubated in the presence of 5.5 mM glucose. The protective effect of glucose against apoptosis may be mediated by maintenance of the intracellular ATP concentration.
Healy
Declan A
DA
Department of Biochemistry, University College Dublin, Belfield, Dublin 4, Ireland.
Watson
R William G
RW
Newsholme
Philip
P
D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D005973:Glutamine / Q000494:pharmacology*; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D019014:fas Receptor / Q000494:pharmacology
D019014:fas Receptor; D005973:Glutamine; D000255:Adenosine Triphosphate; D003847:Deoxyglucose; D005947:Glucose