title: In vitro effect of advanced glycation end-products on human polymorphonuclear superoxide production.
abstract: 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.
authors.affiliation: Department of Nephrology, Sapir Medical Center, Kfar-Saba, Israel.
authors.forename: J
authors.initials: J
authors.lastname: Bernheim
authors.forename: G
authors.initials: G
authors.lastname: Rashid
authors.forename: R
authors.initials: R
authors.lastname: Gavrieli
authors.forename: Z
authors.initials: Z
authors.lastname: Korzets
authors.forename: B
authors.initials: B
authors.lastname: Wolach
mesh_terms: 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*
chemical_list: 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