A NOVEL ROLE FOR THE BETA-2 INTEGRIN CD11B CD18 IN NEUTROPHIL APOPTOSIS - A HOMEOSTATIC MECHANISM IN INFLAMMATION/

In mice selectively deficient in CD11b/CD18, a beta 2 integrin, chemoa ttractant-induced leukocyte adhesion to microvascular endothelium in v ivo was reduced. Paradoxically, thioglycollate-induced neutrophil accu mulation in the peritoneal cavity was increased and was associated wit h a significant delay in apoptosis of extravasated cells. The extravas ated cells had a near absence of neutrophil phagocytosis and a reducti on in oxygen free radical generation, which may contribute to the obse rved defect in apoptosis, This is supported by our in vitro studies, i n which phagocytosis of opsonized particles by human neutrophils rapid ly induced apoptosis that could be blocked with CD11b/CD18 antibodies, Reactive oxygen species are the intracellular link in this process: p hagocytosis-induced apoptosis was blocked both in neutrophils treated with the flavoprotein inhibitor diphenylene iodonium and in neutrophil s from patients with chronic granulomatous disease, which lack NADPH o xidase. Thus, CD11b/CD18 plays a novel and unsuspected homeostatic rol e in inflammation by accelerating the programmed elimination of extrav asated neutrophils.