Differential role of neutrophil Fcγ receptor IIIB (CD16) in phagocytosis, bacterial killing, and responses to immune complexes

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Abstract
Objective: To determine the roles played by the neutrophil Fcγ receptor type II (FcγRII) (CD32) and FcγRIIIb (CD16) in phagocytosis, bacterial killing, and activation by immune complexes (ICs) and to test the hypothesis that inhibition of pathologic effector neutrophil function is possible without compromising host defense.Methods: Receptor function was probed by enzymic removal of FcγRIIIb from the cell surface and by use of Fab/F(ab‘)2 fragments of monoclonal antibodies to block receptor‐ligand binding. Cells were challenged with (a) serum‐opsonized Staphylococcus aureus, (b) serum‐ and IgG‐opsonized latex particles, and (c) synthetic soluble and insoluble ICs to mimic bacterial and inflammatory stimuli.Results: Phosphatidylinositol‐phospholipase C treatment removed >97% of surface FcγRIIIb from neutrophils previously treated with tumor necrosis factor α to mobilize intracellular stores of receptor. This treatment profoundly inhibited activation of primed neutrophils by soluble ICs of the type found in diseased rheumatoid joints, but had no effect on phagocytosis and killing of serum‐opsonized S aureus.Conclusion: FcγRIIIb plays a major role in the secretion of toxic products in response to ICs, but little or no role in the phagocytosis and killing of serum‐opsonized bacteria. The selective suppression of effector neutrophil function is therefore possible. FcγRIIIb, or its intracellular signaling pathway, is a potential therapeutic target in inflammatory diseases such as rheumatoid arthritis, because disruption of its function should decrease inflammatory tissue damage, but not jeopardize host protection against infection.