Helmy Karim Y, Katschke Kenneth J, Gorgani Nick N, Kljavin Noelyn M, Elliott J Michael, Diehl Lauri, Scales Suzie J, Ghilardi Nico, van Lookeren Campagne Menno
Department of Immunology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Cell. 2006 Mar 10;124(5):915-27. doi: 10.1016/j.cell.2005.12.039.
The complement system serves an important role in clearance of pathogens, immune complexes, and apoptotic cells present in the circulation. Complement fragments deposited on the particle surface serve as targets for complement receptors present on phagocytic cells. Although Kupffer cells, the liver resident macrophages, play a dominant role in clearing particles in circulation, complement receptors involved in this process have yet to be identified. Here we report the identification and characterization of a Complement Receptor of the Immunoglobulin superfamily, CRIg, that binds complement fragments C3b and iC3b. CRIg expression on Kupffer cells is required for efficient binding and phagocytosis of complement C3-opsonized particles. In turn, Kupffer cells from CRIg-deficient mice are unable to efficiently clear C3-opsonized pathogens in the circulation, resulting in increased infection and mortality of the host. CRIg therefore represents a dominant component of the phagocytic system responsible for rapid clearance of C3-opsonized particles from the circulation.
补体系统在清除循环系统中存在的病原体、免疫复合物和凋亡细胞方面发挥着重要作用。沉积在颗粒表面的补体片段可作为吞噬细胞上补体受体的靶点。尽管肝内巨噬细胞库普弗细胞在清除循环中的颗粒方面起主导作用，但参与这一过程的补体受体尚未得到鉴定。在此，我们报告了免疫球蛋白超家族补体受体CRIg的鉴定和特征，该受体可结合补体片段C3b和iC3b。库普弗细胞上的CRIg表达是补体C3调理颗粒有效结合和吞噬所必需的。反过来，CRIg缺陷小鼠的库普弗细胞无法有效清除循环中的C3调理病原体，导致宿主感染增加和死亡率上升。因此，CRIg代表了吞噬系统的一个主要成分，负责从循环中快速清除C3调理颗粒。
