C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific
Mary-Pat Stein, … , Carolyn Mold, Terry W. Du Clos
Mary-Pat Stein, … , Carolyn Mold, Terry W. Du Clos
Published February 1, 2000
Citation Information: J Clin Invest. 2000;105(3):369-376. https://doi.org/10.1172/JCI7817.
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Article

C-reactive protein binding to FcγRIIa 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. FcγRIa, the high-affinity IgG receptor, binds CRP with low affinity, whereas FcγRIIa, the low-affinity IgG receptor, binds CRP with high affinity. Because the single nucleotide polymorphism in FcγRIIA — 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 FcγRIIA R-131 homozygotes, and binding was inhibited by the R-specific mAb 41H16. CRP showed decreased binding to cells from FcγRIIA H-131 homozygotes (which bind IgG2 with high affinity). However, IFN-γ enhanced FcγRI expression by H-131 monocytes and increased CRP binding. FcγRIIa heterozygotes showed intermediate binding. CRP initiated increases in [Ca2+]i in PMN from R-131, but not from H-131 homozygotes. These data provide direct genetic evidence for FcγRIIa 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 FcγRIIA alleles to host defense and autoimmunity.

Authors

Mary-Pat Stein, Jeffrey C. Edberg, Robert P. Kimberly, Erin K. Mangan, Dwaipayan Bharadwaj, Carolyn Mold, Terry W. Du Clos

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CRP binding to human monocytes and PMN from R-131 homozygous donors is i...
CRP binding to human monocytes and PMN from R-131 homozygous donors is inhibited by mAb 41H16. Washed, anticoagulated whole blood was prepared from R-131 homozygotes. Aliquots of the washed blood were incubated with the anti-FcγRIIa mAb 41H16 or with a mIgG2a isotype control for 15 minutes at 4°C. CRP (100 μg/mL) was added, and the incubation was continued for an additional 60 min. After 2 washes, bound CRP was detected with the anti-CRP mAb 2C10-FITC. The shaded area represents background binding of the mAb 2C10-FITC only. (a) Neutrophils; (b) monocytes.