title: Complement receptor of the Ig superfamily enhances complement-mediated phagocytosis in a subpopulation of tissue resident macrophages.
abstract: 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 Ca(2+) and Mg(2+), which differs from the beta(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.
authors.affiliation: Department of Immunology, Genentech, South San Francisco, CA 94080, USA.
authors.forename: Nick N
authors.initials: NN
authors.lastname: Gorgani
authors.forename: Jeannie Q
authors.initials: JQ
authors.lastname: He
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Katschke
authors.forename: Karim Y
authors.initials: KY
authors.lastname: Helmy
authors.forename: Hongkang
authors.initials: H
authors.lastname: Xi
authors.forename: Micah
authors.initials: M
authors.lastname: Steffek
authors.forename: Philip E
authors.initials: PE
authors.lastname: Hass
authors.forename: Menno
authors.initials: M
authors.lastname: van Lookeren Campagne
mesh_terms: D000818:Animals; D018821:CD18 Antigens / Q000276:immunology; D002118:Calcium / Q000276:immunology; D003176:Complement C3 / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D008024:Ligands; D008264:Macrophages / Q000276:immunology*; D008274:Magnesium / Q000276:immunology; D051379:Mice; D008806:Mice, Inbred AKR; D018345:Mice, Knockout; D010587:Phagocytosis / Q000276:immunology*; D011951:Receptors, Complement / Q000819:agonists / Q000276:immunology*
chemical_list: D018821:CD18 Antigens; D003176:Complement C3; D008024:Ligands; D011951:Receptors, Complement; C509992:VSIG4 protein, mouse; D008274:Magnesium; D002118:Calcium