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

J. Bernheim*, G. Rashid, R. Gavrieli, Z. Korzets, B. Wolach

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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. 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.

Original languageEnglish
Pages (from-to)1064-1069
Number of pages6
JournalEuropean Journal of Clinical Investigation
Issue number12
StatePublished - 2001


  • Advanced glycation end-products
  • Polymorphonuclear leukocytes
  • Superoxide anion


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