Roos Anja, Xu Wei, Castellano Giuseppe, Nauta Alma J, Garred Peter, Daha Mohamed R, van Kooten Cees
Department of Nephrology, Leiden University Medical Center, Leiden, The Netherlands.
Eur J Immunol. 2004 Apr;34(4):921-9. doi: 10.1002/eji.200424904.
Apoptotic cells can be recognized and taken up by both macrophages and dendritic cells. Phagocytosis of apoptotic cells generally leads to active suppression of cytokine production by professional phagocytes. This is different from the response towards cells that die by necrosis, which induce a pro-inflammatory cytokine profile. Uptake of apoptotic cells involves a large number of receptors and opsonins, which bind to cellular ligands exposed during the various stages of apoptotic cell death. Among the opsonins of apoptotic cells, complement factors, including C1q, and complement-activating members of the pentraxin family play an important role. This is indicated by in vitro phagocytosis studies and supported by the susceptibility to systemic autoimmunity of carriers of genetic deficiencies for early complement proteins. The present review summarizes the role of molecules of innate immunity in the handling of apoptotic cells by macrophages and dendritic cells. It is proposed that C1q and other opsonins prevent autoimmunity and maintain self-tolerance by supporting the efficient clearance of apoptotic material, as well as by actively modulating phagocyte function.
凋亡细胞可被巨噬细胞和树突状细胞识别并吞噬。凋亡细胞的吞噬作用通常会导致专业吞噬细胞对细胞因子产生的主动抑制。这与对坏死细胞的反应不同，坏死细胞会诱导促炎细胞因子谱。凋亡细胞的摄取涉及大量受体和调理素，它们与凋亡细胞死亡各个阶段暴露的细胞配体结合。在凋亡细胞的调理素中，补体因子，包括C1q，以及五聚体蛋白家族的补体激活成员发挥着重要作用。体外吞噬研究表明了这一点，并得到早期补体蛋白基因缺陷携带者对系统性自身免疫易感性的支持。本综述总结了固有免疫分子在巨噬细胞和树突状细胞处理凋亡细胞中的作用。有人提出，C1q和其他调理素通过支持凋亡物质的有效清除以及通过积极调节吞噬细胞功能来预防自身免疫并维持自身耐受性。
