Gershov D, Kim S, Brot N, Elkon K B
Hospital for Special Surgery, Weill Medical College of Cornell University, New York, New York 10021, USA.
J Exp Med. 2000 Nov 6;192(9):1353-64. doi: 10.1084/jem.192.9.1353.
C-reactive protein (CRP) is a serum protein that is massively induced as part of the innate immune response to infection and tissue injury. As CRP has been detected in damaged tissues and is known to activate complement, we assessed whether apoptotic lymphocytes bound CRP and determined the effect of binding on innate immunity. CRP bound to apoptotic cells in a Ca(2+)-dependent manner and augmented the classical pathway of complement activation but protected the cells from assembly of the terminal complement components. Furthermore, CRP enhanced opsonization and phagocytosis of apoptotic cells by macrophages associated with the expression of the antiinflammatory cytokine transforming growth factor beta. The antiinflammatory effects of CRP required C1q and factor H and were not effective once cells had become necrotic. These observations demonstrate that CRP and the classical complement components act in concert to promote noninflammatory clearance of apoptotic cells and may help to explain how deficiencies of the classical pathway and certain pentraxins lead to impaired handling of apoptotic cells and increased necrosis with the likelihood of immune response to self.
C反应蛋白（CRP）是一种血清蛋白，作为对感染和组织损伤的固有免疫反应的一部分被大量诱导产生。由于在受损组织中已检测到CRP，并且已知其可激活补体，我们评估了凋亡淋巴细胞是否结合CRP，并确定了结合对固有免疫的影响。CRP以Ca(2+)依赖的方式与凋亡细胞结合，增强补体激活的经典途径，但保护细胞免受末端补体成分的组装。此外，CRP增强了巨噬细胞对凋亡细胞的调理作用和吞噬作用，这与抗炎细胞因子转化生长因子β的表达相关。CRP的抗炎作用需要C1q和因子H，一旦细胞发生坏死则无效。这些观察结果表明，CRP和经典补体成分协同作用以促进凋亡细胞的非炎性清除，这可能有助于解释经典途径和某些五聚体蛋白的缺陷如何导致凋亡细胞处理受损以及坏死增加，并有可能引发自身免疫反应。
