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 th e 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 func tion, we have analyzed the effect of AGE-modified proteins on PMA-depe ndent superoxide anion production (O-2 .(-)) from normal rat peritonea l 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, f ully prevents the effect of AGE-BSA in vitro. Macrophages from diabeti c rats shown an inhibition on PMA dependent-O-2 .(-) production. Howev er, the treatment in vivo with aminoguanidine produced a cancelation o f the inhibitory effect observed in the diabetic state. These data sug gest that AGE-modified proteins could be implicated in the impairement of macrophage respiratory burst in diabetes.