title: C-reactive protein binding to FcgammaRIIa on human monocytes and neutrophils is allele-specific.
abstract: C-reactive protein (CRP) is involved in host defense, regulation of inflammation, and modulation of autoimmune disease. Although the presence of receptors for CRP on phagocytes has been inferred for years, their identity was determined only recently. FcgammaRIa, the high-affinity IgG receptor, binds CRP with low affinity, whereas FcgammaRIIa, the low-affinity IgG receptor, binds CRP with high affinity. Because the single nucleotide polymorphism in FcgammaRIIA - which encodes histidine or arginine at position 131 - strongly influences IgG2 binding, we determined this polymorphism's effect on CRP binding. CRP bound with high avidity to monocytes and neutrophils from FcgammaRIIA R-131 homozygotes, and binding was inhibited by the R-specific mAb 41H16. CRP showed decreased binding to cells from FcgammaRIIA H-131 homozygotes (which bind IgG2 with high affinity). However, IFN-gamma enhanced FcgammaRI expression by H-131 monocytes and increased CRP binding. FcgammaRIIa heterozygotes showed intermediate binding. CRP initiated increases in [Ca(2+)](i) in PMN from R-131, but not from H-131 homozygotes. These data provide direct genetic evidence for FcgammaRIIa as the functional, high-affinity CRP receptor on leukocytes while emphasizing the reciprocal relationship between IgG and CRP binding avidities. This counterbalance may affect the contribution of FcgammaRIIA alleles to host defense and autoimmunity.
authors.affiliation: Department of Medicine, University of New Mexico School of Medicine, Albuquerque, New Mexico 87108, USA.
authors.forename: M P
authors.initials: MP
authors.lastname: Stein
authors.forename: J C
authors.initials: JC
authors.lastname: Edberg
authors.forename: R P
authors.initials: RP
authors.lastname: Kimberly
authors.forename: E K
authors.initials: EK
authors.lastname: Mangan
authors.forename: D
authors.initials: D
authors.lastname: Bharadwaj
authors.forename: C
authors.initials: C
authors.lastname: Mold
authors.forename: T W
authors.initials: TW
authors.lastname: Du Clos
mesh_terms: D000483:Alleles; D015703:Antigens, CD / Q000235:genetics* / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D002478:Cells, Cultured; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D009000:Monocytes / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*; D011485:Protein Binding; D017452:Receptors, IgG / Q000235:genetics* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C080568:Fc gamma receptor IIA; D017452:Receptors, IgG; D002097:C-Reactive Protein