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Complement Receptor of the Ig Superfamily Enhances Complement-Mediated Phagocytosis in a Subpopulation of Tissue Resident Macrophages

Nick N. Gorgani^1,*, Jeannie Q. He^1,*, Kenneth J. Katschke, Jr.^*, Karim Y. Helmy^*, Hongkang Xi^*, Micah Steffek, Philip E. Hass and Menno van Lookeren Campagne^2,*

^* Department of Immunology, Protein Engineering, and Protein Chemistry, Genentech, South San Francisco, CA 94080

An important function of the complement cascade is to coat self and foreign particles with C3-proteins that serve as ligands for phagocytic receptors. Although tissue resident macrophages play an important role in complement-mediated clearance, the receptors coordinating this process have not been well characterized. In the present study, we identified a subpopulation of resident peritoneal macrophages characterized by high expression of complement receptor of the Ig superfamily (CRIg), a recently discovered complement C3 receptor. Macrophages expressing CRIg showed significantly increased binding and subsequent internalization of complement-opsonized particles compared with CRIg negative macrophages. CRIg internalized monovalent ligands and was able to bind complement-opsonized targets in the absence of Ca²⁺ and Mg²⁺, which differs from the β₂-integrin CR3 that requires divalent cations and polyvalent ligands for activation of the receptor. Although CRIg dominated in immediate binding of complement-coated particles, CRIg and CR3 contributed independently to subsequent particle phagocytosis. CRIg thus identifies a subset of tissue resident macrophages capable of increased phagocytosis of complement C3-coated particles, a function critical for immune clearance.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ N.N.G. and J.Q.H. contributed equally to the work.

² Address correspondence and reprint requests to Menno van Lookeren Campagne, Genentech, 1 DNA Way, South San Francisco, CA 94080. E-mail address: menno{at}gene.com

³ Abbreviations used in this paper: CR, complement receptor; CRIg, CR of the Ig superfamily; RPM, resident peritoneal macrophage; naRPM, nonadherent RPM; adRPM, adherent RPM; 7-AAD, 7-aminoactinomycin D; HGDMEM, high glucose DMEM; E-IgM, IgM-coated erythrocyte; EAC, complement-opsonized E-IgM; SRBC, sheep RBC; Crry, CR-related gene Y; MFI, mean fluorescent intensity; DAPI, 4',6-diamidino-2-phenylindole.