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 end-products 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.


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.
Bernheim
J
J
Department of Nephrology, Sapir Medical Center, Kfar-Saba, Israel.
Rashid
G
G
Gavrieli
R
R
Korzets
Z
Z
Wolach
B
B
D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010084:Oxidation-Reduction; D012710:Serum Albumin, Bovine / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism*
D017127:Glycation End Products, Advanced; C081628:advanced glycation end products-bovine serum albumin; D013481:Superoxides; D012710:Serum Albumin, Bovine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D005947:Glucose