Inhibitory effect of albumin-derived advanced glycosylation products on PMA-induced superoxide anion production by rat macrophages

Advanced glycosylation end products (AGE) are implicated in many of the complications of diabetes. In the same way, infectious diseases are frequently associated with this disease. An impaired respiratory burst in macrophages may be a cause of infectious complications in diabetic patients. To establish a possible mechanism of this altered cell function, we have analyzed the effect of AGE-modified proteins on PMA-dependent superoxide anion production (O2.-) from normal rat peritoneal macrophages. We have used AGE-modified bovine serum albumin (AGE-BSA) prepared by incubation with glucose. AGE-BSA partially inhibits the phorbol ester-dependent superoxide production by macrophages in vitro. The specificity of this inhibitory effect is demonstrated by the fact that aminoguanidine, an inhibitor of the formation of AGE products, fully prevents the effect of AGE-BSA in vitro. Macrophages from diabetic rats shown an inhibition on PMA dependent-O2.- production. However, the treatment in vivo with aminoguanidine produced a cancelation of the inhibitory effect observed in the diabetic state. These data suggest that AGE-modified proteins could be implicated in the impairment of macrophage respiratory burst in diabetes.