Fabriek Babs O, van Bruggen Robin, Deng Dong Mei, Ligtenberg Antoon J M, Nazmi Kamran, Schornagel Karin, Vloet Rianka P M, Dijkstra Christine D, van den Berg Timo K
Department of Molecular Cell Biology and Immunology, VU Medical Center, Amsterdam.
Blood. 2009 Jan 22;113(4):887-92. doi: 10.1182/blood-2008-07-167064. Epub 2008 Oct 10.
The plasma membrane glycoprotein receptor CD163 is a member of the scavenger receptor cystein-rich (SRCR) superfamily class B that is highly expressed on resident tissue macrophages in vivo. Previously, the molecule has been shown to act as a receptor for hemoglobin-haptoglobin complexes and to mediate cell-cell interactions between macrophages and developing erythroblasts in erythroblastic islands. Here, we provide evidence for a potential role for CD163 in host defense. In particular, we demonstrate that CD163 can function as a macrophage receptor for bacteria. CD163 was shown to bind both Gram-positive and -negative bacteria, and a previously identified cell-binding motif in the second scavenger domain of CD163 was sufficient to mediate this binding. Expression of CD163 in monocytic cells promoted bacteria-induced proinflammatory cytokine production. Finally, newly generated antagonistic antibodies against CD163 were able to potently inhibit cytokine production elicited by bacteria in freshly isolated human monocytes. These findings identify CD163 as a macrophage receptor for bacteria and suggest that, during bacterial infection, CD163 on resident tissue macrophages acts as an innate immune sensor and inducer of local inflammation.
质膜糖蛋白受体CD163是富含半胱氨酸的清道夫受体（SRCR）超家族B类成员，在体内驻留组织巨噬细胞上高度表达。此前，该分子已被证明是血红蛋白-触珠蛋白复合物的受体，并介导成红细胞岛中巨噬细胞与发育中的成红细胞之间的细胞间相互作用。在此，我们提供证据表明CD163在宿主防御中具有潜在作用。特别是，我们证明CD163可作为巨噬细胞的细菌受体。CD163被证明能结合革兰氏阳性菌和阴性菌，并且CD163第二个清道夫结构域中先前鉴定的细胞结合基序足以介导这种结合。单核细胞中CD163的表达促进了细菌诱导的促炎细胞因子的产生。最后，新产生的抗CD163拮抗抗体能够有效抑制新鲜分离的人单核细胞中细菌引发的细胞因子产生。这些发现确定CD163为巨噬细胞的细菌受体，并表明在细菌感染期间，驻留组织巨噬细胞上的CD163作为先天性免疫传感器和局部炎症诱导剂发挥作用。
