Different abilities of two types of Fc gamma receptor on guinea-pig macrophages to trigger the intracellular Ca2+ mobilization and O2- generation.

When exposed to hen ovalbumin (OA)-complexed IgG antibodies, guinea-pig macrophages undergo O2- generation and a rapid rise in the intracellular concentration of free Ca2+ ((Ca2+]i). These responses were found to depend on the IgG isotype of antibodies used; OA-complexed IgG2 antibody (OA gamma 2) induced these responses 3-5 times more intensively than did OA-complexed IgG1 antibody (OA gamma 1). The inhibitory effects of monoclonal antibody to Fc gamma receptor for IgG2 alone (Fc gamma 2R) and that to Fc gamma receptor for both IgG1 and IgG2 (Fc gamma 1/gamma 2R) showed that Fc gamma 2R triggered both an increase in [Ca2+]i and activation of the respiratory burst NADPH oxidase more effectively than did Fc gamma 1/gamma 2R. As the number of Fc gamma 2R molecules per macrophage is about one-half that of Fc gamma 1/gamma 2R molecules, the ability of Fc gamma 2R to trigger these responses may be much higher than that of Fc gamma 1/gamma 2R. This difference between their abilities was further demonstrated by measuring the responses induced by cross-linking of Fc gamma 2R or Fc gamma 1/gamma 2R molecules. In addition, the O2- generation with OA gamma 1 was found to be enhanced with cytochalasin B, and to be lowered by depletion of the intracellular Ca2+ of macrophages with Ionomycin and EGTA, though cytochalasin B and the Ca2+ depletion did not affect the O2- generation with OA gamma 2. These results suggest that the mechanisms of Fc gamma 2- and Fc gamma 1/gamma 2 R-mediated signal transmission leading to activation of the NADPH oxidase also differ from each other.