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

Human monocyte/macrophages (Mphi) exposed to nonparticulate stimuli can express cell surface Fas ligand (FasL) and release active soluble FasL (sFasL). We now report that monocyte/Mphi-ingesting opsonized zymosan released sFasL and conditioned supernatants so that these triggered Fas-mediated apoptosis of "bystander" monocytes and FasL-negative neutrophils. Furthermore, identical results were seen with Mphi taking up apoptotic neutrophils, whereas medium conditioned by Mphi phagocytizing latex beads had no proapoptotic effects upon neutrophils despite the presence of sFasL. These data suggest the hitherto unrecognized existence of a feedback loop requiring soluble 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.