Regulation of Fc gamma 2a receptor-mediated phagocytosis by a murine macrophage-like cell line, P388D1: involvement of casein kinase II activity associated with Fc gamma 2a receptor.

A question of whether or not casein kinase II (CKII) activity associated with Fc gamma 2aR is involved in the regulation of phagocytic process mediated by this type of Fc gamma R was investigated. Our previous studies showed that the rate of phagocytosis of sheep erythrocytes (SRBC) coated with anti-SRBC antibody (EA) by P388D1 cells varies significantly depending on the isotypes of antibody and that Fc gamma 2aR isolated from the detergent lysate of P388D1 cells is associated with CKII activity, whereas Fc gamma 2bR is not. Fc gamma Rs-mediated phagocytosis is a major function of macrophages by which invading pathogens such as bacteria could be eliminated and therefore warrants the investigation of its biochemical mechanisms. We have recently shown that phagocytosis of EA2b mediated by Fc gamma 2bR of P388D1 cells as well as murine peritoneal macrophages could be up-regulated by promoting the association of various cytoskeletal components with the receptor by inhibiting Fc gamma 2bR-associated phospholipase A2 (PLA2). CKII activity-associated Fc gamma 2aR mediates phagocytosis of EA2a more effectively than PLA2-associated Fc gamma 2bR mediates phagocytosis of EA2b. We have therefore examined a potential role of CKII in Fc gamma 2aR-mediated phagocytosis by the use of a specific inhibitor of CKII activity (heparin). Results showed that heparin inhibited CKII activity associated with Fc gamma 2aR and effectively down-regulated the Fc gamma 2aR-mediated phagocytosis by apparently blocking the association of the receptor with four types of cytoskeletal components (actin-binding protein, myosin heavy chain, alpha tubulin, and actin).(ABSTRACT TRUNCATED AT 250 WORDS)