C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific
C-reactive protein binding to FcγRIIa on human monocytes and neutrophils is allele-specific
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DOI：
10.1172/jci7817
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发表时间：
2000-02-01
影响因子：
15.9
通讯作者：
Du Clos, TW
中科院分区：
文献类型：
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作者：
Stein, MP;Edberg, JC;Du Clos, TW
C-反应蛋白（CRP）参与宿主防御、炎症调节和自身免疫性疾病的调节。尽管吞噬细胞上CRP受体的存在已被推断多年，但它们的身份仅在最近才被确定。Fc γ RIa（高亲和力IgG受体）以低亲和力结合CRP，而Fc γ RIIa（低亲和力IgG受体）以高亲和力结合CRP。由于Fc γ RIIA的单核苷酸多态性（编码131位的组氨酸或精氨酸）强烈影响IgG 2结合，我们确定了该多态性对CRP结合的影响。CRP与Fc γ RIIA R-131纯合子的单核细胞和中性粒细胞以高亲合力结合，并且结合被R特异性mAb 41 H16抑制。CRP显示与来自Fc γ RIIA H-131纯合子（其以高亲和力结合IgG 2）的细胞的结合降低。然而，IFN-γ增强H-131单核细胞的Fc γ RI表达并增加CRP结合。Fc γ RIIa杂合子显示中间结合。CRP引起R-131的PMN [Ca ~（2+）]（i）增加，但不引起H-131纯合子的PMN [Ca ~（2+）]（i）增加。这些数据为Fc γ RIIa作为白细胞上的功能性、高亲和力CRP受体提供了直接的遗传学证据，同时强调了IgG和CRP结合亲和力之间的相互关系。这种平衡可能影响Fc γ RIIA等位基因对宿主防御和自身免疫的贡献。
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. Fc gamma RIa, the high-affinity IgG receptor, binds CRP with low affinity, whereas Fc gamma RIIa, the low-affinity IgG receptor, binds CRP with high affinity. Because the single nucleotide polymorphism in Fc gamma RIIA-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 Fc gamma RIIA R-131 homozygotes, and binding was inhibited by the R-specific mAb 41H16. CRP showed decreased binding to cells from Fc gamma RIIA H-131 homozygotes (which bind IgG2 with high affinity). However, IFN-gamma enhanced Fc gamma RI expression by H-131 monocytes and increased CRP binding. Fc gamma RIIa 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 Fc gamma RIIa 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 Fc gamma RIIA alleles to host defense and autoimmunity.