Interaction of Two Phagocytic Host Defense Systems Fcγ RECEPTORS AND COMPLEMENT RECEPTOR 3

Phagocytosis of foreign pathogens by cells of the immune system is a vitally important function of innate immunity. The phagocytic response is initiated when ligands on the surface of invading microorganisms come in contact with receptors on the surface of phagocytic cells such as neutrophils, monocytes/macrophages, and dendritic cells. The complement receptor CR3 (CD11b/CD18, Mac-1) mediates the phagocytosis of complement protein (C3bi)-coated particles. Fc gamma receptors (Fc gamma Rs) bind IgG-opsonized particles and provide a mechanism for immune clearance and phagocytosis of IgG-coated particles. We have observed that stimulation of Fc gamma Rs modulates CR3-mediated phagocytosis and that Fc gamma RIIA and Fc gamma RI exert opposite (stimulatory and inhibitory) effects. We have also determined that an intact Fc gamma R immunoreceptor tyrosine-based activation motif is required for these effects, and we have investigated the involvement of downstream effectors. The ability to up-regulate or down-regulate CR3 signaling has important implications for therapeutics in disorders involving the host defense system.