Ability of Neutrophils to Produce Active Oxygen Species in Diabetic Patients

Abstract

The stimulated productions of superoxide anion in polymorphonuclear leukocytes obtained from diabetic patients and control subjects were measured. Superoxide production was estimated with a flowcytometer by measuring oxidized fluorescent products of 2, 7-dichlorofluorescin diacetate incorporated in leukocytes.
The superoxide production stimulated by phorbol myristate acetate (PMA) was significantly less in diabetic patient's leukocytes than in control subjects' leukocytes (mean±SE 12900±257 versus 11400±463 counts; p<0.01), and that stimulated by opsonized zymozan also tended to be less in diabetic patients' leukocytes than in those of control subjects. The PMA stimulated polymorphonuclear leukocytes was negatively correlated with fasted blood glucose levels in the diabetic patients (r=-0.500, p<0.05), but not with glycated protein marker levels.
Stimulated superoxide production in polymorphonuclear leukocytes decreased after incubation with glucose at concentrations between 20 to 50mmo1/1 (p<0.05).
We conclude that stimulated superoxide anion production in polymorphonuclear leukocytes was impaired by hyperglycemia. This impairment may be the consequence of a shrunken NADPH pool depleted via the sorbitol pathway in conditions of hyperglycemia and thought to be one of the reasons for the vulnerability to infection of diabetic patients.