Phagocytosis triggers macrophage release of Fas ligand and induces apoptosis of bystander leukocytes

Human monocyte/macrophages (M phi) exposed to nonparticulate stimuli can ex press cell surface Fas ligand (FasL) and release active soluble Fast (sFasL ). We now report that monocyte/M phi-ingesting opsonized zymosan released s FasL and conditioned supernatants so that these triggered Fas-mediated apop tosis of "bystander" monocytes and Fast-negative neutrophils. Furthermore, identical results were seen with M phi taking up apoptotic neutrophils, whe reas medium conditioned by M phi phagocytizing latex beads had no proapopto tic effects upon neutrophils despite the presence of sFasL. These data sugg est the hitherto unrecognized existence of a feedback loop requiring solubl e factors in addition to sFasL that may promote resolution of inflammation- phagocytic clearance of apoptotic cells leading to Fas-mediated killing of bystander leukocytes by phagocytizing macrophages.