Granulocyte Fc gamma receptor recognition of cell bound and aggregated IgG: effect of gamma-interferon.

Granulocyte Fc gamma receptors are important components in the recognition of IgG-coated cells and immune complexes. Two proteins have been identified on resting human granulocytes which function as Fc gamma receptors, Fc gamma RII (CD32) and Fc gamma RIII (CD16). A third protein, Fc gamma RI (CD64), is not constitutively expressed on resting granulocytes, but can be induced by activation with gamma-interferon. We examined the role of these three Fc gamma receptors on human granulocytes in the binding of both IgG-sensitized erythrocytes and soluble oligomeric IgG. In these studies we employed anti-Fc gamma receptor antibodies which complete for the Fc gamma RII and Fc gamma RIII ligand binding sites. Preincubation of granulocytes with saturating concentrations of high-affinity anti-Fc gamma RII monoclonal antibody did not alter the recognition of IgG sensitized human cells by granulocytes. Furthermore, ligand binding studies demonstrated that anti-Fc gamma RII antibody altered neither the number nor the affinity of granulocyte binding sites for human trimeric IgG. In contrast, Fab anti-Fc gamma RIII inhibited the binding of both IgG (anti-D) sensitized human RBCs and IgG sensitized sheep RBCs. Similarly, a reduction in the expression of Fc gamma RIII by treatment with phosphatidyl-inositol specific phospholipase C reduced PMN recognition of IgG-sensitized cells. Also, anti-Fc gamma RIII decreased the number of granulocyte binding sites for human IgG trimer without a change in receptor affinity. Fc gamma RI, which was induced by gamma-IFN, increased granulocyte recognition of both IgG sensitized RBCs and IgG trimer. These data suggest that Fc gamma RIII is the primary Fc gamma receptor on granulocytes which recognizes IgG sensitized RBCs and low molecular weight complexes of IgG. With gamma-interferon activated granulocytes, Fc gamma RI appears to enhance this recognition process.