Mold Carolyn, Baca Rebecca, Du Clos Terry W
Department of Molecular Genetics and Microbiology, University of New Mexico School of Medicine, Albuquerque, NM 87108, USA
J Autoimmun. 2002 Nov;19(3):147-54. doi: 10.1006/jaut.2002.0615.
Serum amyloid P component (SAP) and C-reactive protein (CRP) are opsonins that react with nuclear autoantigens targeted in systemic autoimmunity. CRP and SAP bind to apoptotic and necrotic cells, which are potential sources of these autoantigens. We have recently determined that the receptors for CRP on phagocytic cells are Fcgamma receptors. The goal of this study was to determine whether CRP and SAP promote phagocytosis of apoptotic cells and to identify the receptors involved. Apoptosis was induced in human neutrophils (PMN) and the Jurkat T-cell line by UV-irradiation. SAP treatment of apoptotic human PMN increased ingestion by autologous macrophages. Both SAP and CRP increased ingestion of apoptotic, but not normal Jurkat cells by J-774 macrophages and mouse peritoneal macrophages. Neither SAP nor CRP increased ingestion of apoptotic Jurkat cells by macrophages from FcR gamma-chain deficient mice, which lack FcgammaRI and FcgammaRIII. Inhibition of FcgammaRIII-mediated uptake using mAb 2.4G2 eliminated opsonization by SAP, but not by CRP. These results indicate that pentraxins promote uptake of apoptotic cells through FcgammaRI and/or FcgammaRIII. Ingestion through these receptors is expected to alter the pattern of cytokine production and antigen presentation in response to apoptotic cells.
血清淀粉样蛋白P成分（SAP）和C反应蛋白（CRP）是与系统性自身免疫中靶向的核自身抗原发生反应的调理素。CRP和SAP与凋亡细胞和坏死细胞结合，而这些细胞是这些自身抗原的潜在来源。我们最近确定吞噬细胞上CRP的受体是Fcγ受体。本研究的目的是确定CRP和SAP是否促进凋亡细胞的吞噬作用，并鉴定其中涉及的受体。通过紫外线照射在人中性粒细胞（PMN）和Jurkat T细胞系中诱导凋亡。用SAP处理凋亡的人PMN可增加自体巨噬细胞的摄取。SAP和CRP均可增加J-774巨噬细胞和小鼠腹腔巨噬细胞对凋亡的Jurkat细胞而非正常Jurkat细胞的摄取。来自缺乏FcγRI和FcγRIII的FcRγ链缺陷小鼠的巨噬细胞，SAP和CRP均未增加对凋亡Jurkat细胞的摄取。使用单克隆抗体2.4G2抑制FcγRIII介导的摄取可消除SAP的调理作用，但不能消除CRP的调理作用。这些结果表明，五聚蛋白通过FcγRI和/或FcγRIII促进凋亡细胞的摄取。通过这些受体的摄取有望改变对凋亡细胞的细胞因子产生模式和抗原呈递。
