Monoclonal Antibody to the Type II Fc Receptor for Human IgG Blocks Potentiation of Monocyte and Neutrophil IgG-Induced Respiratory Burst Activation by Aggregated C-Reactive Protein

The acute Phase Protein, CRP, when heat-aggregated (Agg-CRP), binds to human monocytes and neutrophils and potentiated the respiratory burst stimulated by heat-aggregated IgG (Agg-IgG). Earlier data from our laboratory and others have indicated that CRP binds to phagocytic cells at membrane sites associated with IgG Fc receptors. The present study utilized monoclonal antibodies (MAb) to determine whether the Agg-CRP potentiation of oxidative metabolism could be linked to activation through FcγRI, FcγRII, or FcγRIII. Preincubation of monocytes with MAb 32.2, which recognizes an FcγRI epitope distinct from its IgG binding site, had only a minimal (20%) inhibitory effect on Agg-IgG-induced luminol chemiluminescence (CL) and exerted no significant effect on its enhancement by Agg-CRP. MAb 10.1, which blocks IgG binding to FcγRI, reduced Agg-IgG-induced monocyte CL by 40%, but did not alter the Agg-CRP-mediated enhancement. In contrast, exposure to MAb IV.3, which binds to FcγRII on monocytes and neutrophils and blocks IgG binding to this receptor, resulted in a greater than 70%, inhibition off Agg-IgG-induced CL and also significantly suppressed the enhancement by Agg-CRP. MAb Leu-11b, which reacts with FcγRIII on neutrophils, reduced Agg-IgG-induced CL by 70% but did not suppress the Agg-CRP potentiation. Preincubation of monocytes and neutrophils with anti-Leu-M1, anti-CR1, or anti-CR3 failed to block Agg-IgG-induced CL or its enhancement by Agg-CRP. Although the potentiating effect or Agg-CRP on Agg-IgG-elicited CL was blocked by MAb IV.3, this antibody failed to reduce binding of Agg-CRP to either monocytes or neutrophils. These results indicate that, although Agg-CRP does not bind to phagocytic cells at the IgG-binding determinant of FcγRII, it alters Agg-IgG-induced cell activation through this receptor.