title: FcgammaRIIa expression with FcgammaRI results in C-reactive protein- and IgG-mediated phagocytosis.
abstract: C-reactive protein (CRP) is a pattern-recognition molecule, which can bind to phosphorylcholine and certain phosphorylated carbohydrates found on the surface of a number of microorganisms. CRP has been shown recently to bind human Fc receptor for immunoglobulin G (IgG; FcgammaR)I and mediate phagocytosis and signaling through the gamma-chain. To date, binding of monomeric CRP to FcgammaRII has been contentious. We demonstrate that erythrocytes opsonized with CRP bind FcgammaRIIa-transfected COS-7 cells. In addition, we demonstrate that FcgammaRI can use FcgammaRIIa R131 and H131 to phagocytose erythrocytes coated with IgG or purified or recombinant CRP in the absence of the gamma-chain. COS-7 cells expressing FcgammaRIIa or FcgammaRI alone did not phagocytose opsonized erythrocytes. Such phagocytosis required the cytoplasmic domain of FcgammaRIIa, as mutation of tyrosine at position 205 and truncation of the cytoplasmic domain from the end of the transmembrane region (position 206), resulting in the loss of the immunoreceptor tyrosine activatory motif, abrogated phagocytosis. FcgammaRIIa R131 was more efficient than FcgammaRIIa H131 at mediating CRP-dependent phagocytosis.
authors.affiliation: University of Surrey, Guildford, Surrey GU2 7HX, UK. k.bodman-smith@surrey.ac.uk
authors.forename: Katherine B
authors.initials: KB
authors.lastname: Bodman-Smith
authors.forename: Rachel E
authors.initials: RE
authors.lastname: Gregory
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Harrison
authors.forename: John G
authors.initials: JG
authors.lastname: Raynes
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004912:Erythrocytes / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007074:Immunoglobulin G / Q000378:metabolism*; D009154:Mutation; D010587:Phagocytosis; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D012756:Sheep; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry
chemical_list: D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D007140:Immunoglobulin Fab Fragments; D007074:Immunoglobulin G; D017452:Receptors, IgG; D011994:Recombinant Proteins; D014443:Tyrosine; D002097:C-Reactive Protein