title: CRIg: a macrophage complement receptor required for phagocytosis of circulating pathogens.
abstract: The complement system serves an important role in clearance of pathogens, immune complexes, and apoptotic cells present in the circulation. Complement fragments deposited on the particle surface serve as targets for complement receptors present on phagocytic cells. Although Kupffer cells, the liver resident macrophages, play a dominant role in clearing particles in circulation, complement receptors involved in this process have yet to be identified. Here we report the identification and characterization of a Complement Receptor of the Immunoglobulin superfamily, CRIg, that binds complement fragments C3b and iC3b. CRIg expression on Kupffer cells is required for efficient binding and phagocytosis of complement C3-opsonized particles. In turn, Kupffer cells from CRIg-deficient mice are unable to efficiently clear C3-opsonized pathogens in the circulation, resulting in increased infection and mortality of the host. CRIg therefore represents a dominant component of the phagocytic system responsible for rapid clearance of C3-opsonized particles from the circulation.
authors.affiliation: Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
authors.forename: Karim Y
authors.initials: KY
authors.lastname: Helmy
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Katschke
authors.forename: Nick N
authors.initials: NN
authors.lastname: Gorgani
authors.forename: Noelyn M
authors.initials: NM
authors.lastname: Kljavin
authors.forename: J Michael
authors.initials: JM
authors.lastname: Elliott
authors.forename: Lauri
authors.initials: L
authors.lastname: Diehl
authors.forename: Suzie J
authors.initials: SJ
authors.lastname: Scales
authors.forename: Nico
authors.initials: N
authors.lastname: Ghilardi
authors.forename: Menno
authors.initials: M
authors.lastname: van Lookeren Campagne
mesh_terms: D000818:Animals; D003176:Complement C3 / Q000276:immunology; D003179:Complement C3b / Q000276:immunology; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D007728:Kupffer Cells / Q000166:cytology / Q000276:immunology; D008088:Listeriosis / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D009895:Opsonin Proteins / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology; D010587:Phagocytosis / Q000502:physiology*; D011485:Protein Binding; D011951:Receptors, Complement / Q000235:genetics / Q000276:immunology*; D017463:Receptors, Complement 3b
chemical_list: C509991:CR1 protein, human; D003176:Complement C3; D009895:Opsonin Proteins; D010446:Peptide Fragments; D011951:Receptors, Complement; D017463:Receptors, Complement 3b; C509992:VSIG4 protein, mouse; D003179:Complement C3b