Fc gamma 2b receptor-mediated phagocytosis by a murine macrophage-like cell line (P388D1) and peritoneal resident macrophages. Up-regulation by the inhibitors of phospholipase A2 and cyclooxygenase.

Abstract

The mechanisms of Fc gamma R-mediated phagocytosis of immune complexes were investigated by the use of a murine macrophage-like cell line (P388D1) and murine peritoneal resident macrophages. About 40 to 80% of P388D1 cells phagocytosed SRBC coated with IgG2a subclass anti-SRBC mAb (EA2a) within 60 min, whereas only 10 to 20% of the cells phagocytosed EA2b during the same period. The treatment of P388D1 cells with inhibitors of phospholipase A2 (p-bromophenacylbromide, EGTA, or dexamethasone) or of cyclooxygenase (indomethacin or aspirin) significantly promoted the Fc gamma 2bR-mediated phagocytosis of EA2b, but did not affect the Fc gamma 2aR-mediated phagocytosis of EA2a. These results suggest that the activation of phospholipase A2 activity associated with Fc gamma 2bR may lead to the inhibition of phagocytosis of EA2b. This inhibition appeared to be due to the blockade of the interaction of Fc gamma 2bR with various cytoskeletal components, because the association of Fc gamma 2bR and these cytoskeletal components, which could be eliminated by cytochalasin D, was found to be increased by the inhibition of phospholipase A2 activity.