The Different Roles of Two Distinct Fcγ Receptors on Guinea Pig Macrophages in the Phagocytosis of Sensitized Sheep Erythrocytes¹

The functional roles of two distinct types of Fcγ receptors (Fcγ₁/γ₂R specific for both IgG1 and IgG2, and Fcγ₂R specific for IgG2 alone) on the surface of guinea pig macrophages in the phagocytosis of sensitized sheep erythrocytes (EA) were investigated by the use of two Fab′s of monoclonal anti-Fcγ₁/γ₂R and anti-Fcγ₂ R antibodies. The binding and subsequent ingestion of IgG1 antibody-sensitized erythrocytes (EAγ₁) by macrophages were completely inhibited by anti-Fcγ₁/γ₂R Fab′, indicating that the reactions are mediated only by Fcγ₁/γ₂R. On the other hand, the binding and subsequent ingestion of IgG2 antibody-sensitized erythrocytes (EAγ₂) were substantially inhibited by anti-Fcγ₂R Fab′, but not by anti-Fcγ₁/γ₂R Fab′. The inhibitory activities of anti-Fcγ₂R Fab′ were dependent upon the amount of IgG2 antibody bound on erythrocytes; increasing the amount of bound IgG2 antibody from 0.15 to 0.91 µg/2×10⁸ erythroeytes resulted in a decrease in the inhibition of binding of EAγ₂ by anti-Fcγ₂R Fab′ from 50 to 0%, and also a decrease in the inhibition of ingestion of EAγ₂ from 100 to 50%. Since the binding and the ingestion of EAγ₂ by macrophages were completely inhibited in the presence of both anti-Fcγ₂R and anti-Fcγ₁/γ₂R Fab′, Fcγ₂ seems to preferentially operate in these reactions, and Fcγ₁/γ₂R does not seem to operate unless the Fcγ₂R on the same macrophage is blocked by anti-Fcγ₂R Fab′. The finding that the avidity and ingestive activity of macrophages for EAγ₂ are higher than those for EAγ₁ also indicates that Fcγ₂R functions more effectively in the binding and ingestion of EA than Fcγ₁/γ₂R. These different abilities of Fcγ₂R and Fcγ₁/γ₂R do not seem to be caused by any difference in their affinities for EA, since ovalbumin-complexed IgG2 antibody was found to bind to Fcγ₂R with an association constant essentially equal to that to Fcγ₁/γ₂R.