Increased superoxide anion production and glutathione peroxidase activity in peritoneal macrophages from autoimmune-prone MRL/Mp-Ipr/lpr mice.

We studied the release of superoxide anion (O-2) in peritoneal macrophages from autoimmuneprone MRL/Mp-lpr/lpr (MRL/l) mice. Compared to resident peritoneal macrophages from control MRL/Mp-+/+ (MRL/n) mice, macrophages from MRL/l mice exhibited an age-related increase of spontaneous and PMA-induced O-2 secretion in association with the development of the autoimmune process. Analysis of the kinetic parameters of NADPH oxidase in macrophages revealed that MRL/l macrophages were in a primed state, as shown by the decreased Km value of the oxidase for NADPH. Furthermore, we studied several key enzymes for their ability to scavenge the oxygen radicals in the macrophages. Among the enzymes studied, only glutathione peroxidase (GSH Px) activity was increased in peritoneal macrophages from MRL/l mice and this change was closely correlated with the increase in O-2 production. Thus, GSH Px activity in macrophages seems to play an important role in macrophage functions under increased oxidative stress.