|Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1988: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1987: ¥5,100,000 (Direct Cost: ¥5,100,000)
The molecular mechanisms by which phagocytes can recognize and eliminate antigen was studied with guinea pig macrophages and polymorphonuclear leukocytes. The main results obtained are as follows.
1. Both macrophages and leukocytes possess two distinct Fc receptors: FcR_2 for IgG2, and FcR_<1,2> for IgG2 and IgG1.
2. In the binding and ingestion of sensitized erythrocytes by macrophages, FcR_2 was found to function more effectively than FcR_<1,2>. On the contrary, the phagocytosis of immune complexes of protein antigens was similarly mediated by FcR_2 and FcR_<1,2>, but FcR_<1,2> operated predominantly in the reaction, probably due to its larger number than FcR_2. Furthermore, the phagocytosis mediated by FcR_2 ceased within 3 hr, though that by FcR_<1,2> continued at least up to 8 hr. These results indicate that the relative functions of FcR_2 and FcR_<1,2> vary, dependently on the sort of antigen used.
3. FcR_2 on PMN was found to trigger the activation of the respiratory burst NADPH oxidase and phospholipase A_2, but FcR_<1,2> did scarcely so. On the contrary, FcR_<1,2> induced more rapidly and intensively the actin polymerization than FcR_2. FcR_2 and FcR_<1,2>, thus, seem to differ from each other in the mechanism by which they transmit their signal for triggering these responses of PMN.
4. When stimulated with immune complex or C5a, human leukocytes undergo an increase in the concentration of intracellular Ca^<2+> and O^-_ generation. The treatment of cells with pertussis toxin inhibited these responses to C5a, but not those to immune complex, indicating that a different sequence of reactions is involved by immune complex and C5a.
5. The evidence supporting that the NADPH oxidase is composed of the NADPH-cytochrome c reductase and cytochrome b<@2559<@D2 was obtained by reconstitution of the oxidase activity by the purified reductase and cytochrome b<@D2559<@D2.