In vitro effect of advanced glycation end-products on human polymorphonuclear superoxide production

Background Advanced glycation end-products (AGEs) are elevated in the sera of diabetic patients. The latter are prone to severe bacterial infections. Advanced glycation endproducts have been shown to modulate immune competent cell activities, In this study we examined the in vitro effect of advanced glycation end-products on superoxide anion generation by human polymorphonuclear leukocytes. Materials and methods Advanced glycation end-products were prepared by incubation of bovine serum albumin (BSA) with glucose for 90 days. Superoxide production was measured as the superoxide dismutase-inhibitable reduction of ferricytochrome c. The effect of advanced glycation end-products on superoxide production was evaluated in both baseline (nonstimulated) and stimulated (by either formyl-methionyl-leucyl-phenylalanine, or phorbol-myristate-acetate) polymorphonuclear leukocytes. Results The baseline superoxide production of polymorphonuclear leukocytes was significantly increased by advanced glycation end-products in a dose-dependent manner. In contrast, in stimulated polymorphonuclear leukocytes advanced glycation end-products significantly inhibited superoxide production, again in a dose-dependent manner. This inhibitory effect of advanced glycation end-products was observed after dialyzing AGE-BSA, thereby eliminating the possible influence of reactive carbohydrates. No modification of superoxide production was seen with BSA and only a mild inhibitory effect of glucose at high concentrations. Conclusions Advanced glycation end-products depress superoxide production by stimulated polymorphonuclear leukocytes. As superoxide plays an essential role in bactericidal activity, this polymorphonuclear leukocyte dysfunction may be a contributory factor to the increased prevalence and severity of bacterial infection seen in diabetic patients.