|Budget Amount *help
¥6,700,000 (Direct Cost : ¥6,700,000)
Fiscal Year 1990 : ¥2,000,000 (Direct Cost : ¥2,000,000)
Fiscal Year 1989 : ¥4,700,000 (Direct Cost : ¥4,700,000)
The molecular mechanisms by which phagocytes can recognize and eliminate antigens were studied with guinea pig macrophages and polymorphonuclear leukocytes. The main results obtained are as follows. 1. Both macrophages and polymorphonuclear leukocytes were found to possess two distinct Fc receptors : FcR_2 for IgG2, and FcR_<1,2> for both IgG1 and IgG2.2. In the phagocytosis of immune complexes of protein antigens, macrophage FcR_<1,2> operated predominantly, due to its larger number per cell than that of FcR_2, and also to existence of the intracellular pool of FcR_<1,2> For these reasons, the phagocytosis mediated by FcR_<1,2> continued at least up to 8 hr, though that by FcR_2 ceased within 2 hr. 3. The^<1,2> abilities of macrophage FcR_2 to trigger activation of the NADPH oxidasa and phospholipase A_2 were markedly higher than those of FcR_<1,2> . 4. Both the mobilization of Ca^<2+> from its intracellular pool and the phosphatidylinositol turnover were more strongly induced by FcR_2 -mediated stimulation than by FcR_<1,2> -midiated stimulation. 5. The effects of Ca^<2+> depletion with EGTA and Inomycin and of staurosporine revealed that the mechanisms of FcR_2 -and FcR_<1,2> -mediated signal transmission leading to activation of the NADPH oxidase and phospholipase A_2 differed from each other. FcR_2 triggered activation of the NADPH oxidase through the Ca^<2+>-independent pathway, though FcR_<1,2> did through two pathways : the Ca^<2+> -independent and Ca^<2+> -calmodulin pathways. In addition, the activation of phospholipase A_2 through FcR_<1,2> required the Ca^<2+> influx, though that through FcR_2 did not so. 6. The abilities of polymorphonuclear leukocyte FcR_2 to trigger activation of the NADPH oxidase and phospholipase A_2 also were higher than those of FcR_<1,2> due to different mechanisms of FcR_2 -and FcR_<1,2>-mediated signal transmission leading to activation of these enzymes.