Activation of complement by soluble IgG aggregates and their subsequent interaction with macrophages

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The mononuclear phagocyte system (MPS) plays an important role in the removal of both particulate and soluble immunogenic material from the circulation, E.IgG adhere to mononuclear phagocytes if the Fc portion of the IgG can interact with the phagocytes' Fc receptors. Simultaneous sensitization with IgG and C3b enhances the effectiveness of binding and ingestion. If soluble material cannot adhere to the surface of macrophages, it will be endocytosed in vitro via fluid-phase pinocytosis at the concentration that is present in the medium. If the material adheres to the cell's surface via its chemical properties or via specific receptors, it will be selectively concentrated at the cell's surface and endocytosed by an adsorptive pinocytosis. Ingestion of IC via FcγR and C3b depends on the ability of the antibodies to interact with FcγR and their capacity to activate the complement system. IC-bound C3b enhances the adsorptive pinocytosis of IC. Soluble AIgG are also pinocytosed more efficiently when C3b is bound to AIgG. The degree of endocytosis varies with the level of C3b sensitization. The highly effective C3b-mediated pinocytosis can be abolished by treating the macrophages with trypsin to inactivate C3bR. This observation illustrates that C3-mediated pinocytosis can replace Fc-mediated pinocytosis in unstimulated macrophages. Soluble IC and AIgG are removed from the circulation mainly by hepatic Kupffer cells. It seems that the size, the Ag/Ab ratio, the capacity of the IC to bind C1, activate C1, and allow deposition of C3b together with the degree of phagocyte activation determine the degree of binding and subsequent degradation of soluble IC. Further studies on the role of other complement receptors, such as the C1q receptor, are required for a better understanding of the role of complement and complement receptors in the clearance of soluble IC.