title: RAGE binds C1q and enhances C1q-mediated phagocytosis.
abstract: RAGE, the multiligand receptor of the immunoglobulin superfamily of cell surface molecules, is implicated in innate and adaptive immunity. Complement component C1q serves roles in complement activation and antibody-independent opsonization. Using soluble forms of RAGE (sRAGE) and RAGE-expressing cells, we determined that RAGE is a native C1q globular domain receptor. Direct C1q-sRAGE interaction was demonstrated with surface plasmon resonance (SPR), with minimum K(d) 5.6 μM, and stronger binding affinity seen in ELISA-like experiments involving multivalent binding. Pull-down experiments suggested formation of a receptor complex of RAGE and Mac-1 to further enhance affinity for C1q. C1q induced U937 cell adhesion and phagocytosis was inhibited by antibodies to RAGE or Mac-1. These data link C1q and RAGE to the recruitment of leukocytes and phagocytosis of C1q-coated material.
authors.affiliation: Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.
authors.forename: Wanchao
authors.initials: W
authors.lastname: Ma
authors.forename: Vivek
authors.initials: V
authors.lastname: Rai
authors.forename: Barry I
authors.initials: BI
authors.lastname: Hudson
authors.forename: Fei
authors.initials: F
authors.lastname: Song
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Schmidt
authors.forename: Gaetano R
authors.initials: GR
authors.lastname: Barile
mesh_terms: D000911:Antibodies, Monoclonal; D002448:Cell Adhesion; D002460:Cell Line; D003167:Complement Activation; D015922:Complement C1q / Q000276:immunology* / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000276:immunology; D010587:Phagocytosis; D011485:Protein Binding; D000067759:Receptor for Advanced Glycation End Products; D011951:Receptors, Complement / Q000276:immunology; D011971:Receptors, Immunologic / Q000378:metabolism*; D016415:Sequence Alignment; D020298:U937 Cells
chemical_list: D000911:Antibodies, Monoclonal; D016177:Macrophage-1 Antigen; D008562:Membrane Glycoproteins; D000067759:Receptor for Advanced Glycation End Products; D011951:Receptors, Complement; D011971:Receptors, Immunologic; C032402:complement 1q receptor; D015922:Complement C1q