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

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 dis-covered 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 Ca 2 (cid:1) and Mg 2 (cid:1) , which differs from the (cid:2) 2 -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 Journal of Immunology, 2008, 181: 7902–7908. phagocytosis of iC3b-opsonized particles. We further illustrate that the requirements for and ingestion of target particles differ between CRIg (cid:3) and CRIg (cid:4) RPMs.