Human peritoneal macrophage cytotoxicity mediated by cytophilic IgG

Cells of the human mononuclear phagocyte system have recently been shown to possess cytophilic IgG molecules that promote phagocytosis of staphylococci bearing cell-wall protein A. In the present study, the possible mediation of a cytotoxic response to 51Cr-labeled sheep erythrocytes coated with protein A by cytophilic antibodies on human peritoneal macrophages was evaluated. The target cells were readily lysed by peritoneal macrophages. Cytotoxicity was blocked by pretreatment of macrophages with soluble protein or with anti-Fc F(ab')2 fragments. In contrast, cytotoxicity was not affected by cytochalasin B; this finding suggests that cytolysis is an extracellular event. Perturbation of cytophilic IgG with particle-bound protein A elicited a chemiluminescent response from peritoneal macrophages; however, experiments with scavengers of reactive oxygen species indicated that toxic oxygen radicals may not be required for cytotoxicity. The results indicate that cytophilic antibody-mediated cytotoxicity may contribute to cellular injury as well as host-defense aspects of the inflammatory process.