晚期糖基化终产物受体（RAGE）结合 C1q 并增强 C1q 介导的吞噬作用。

RAGE binds C1q and enhances C1q-mediated phagocytosis.

机构信息

Department of Ophthalmology, College of Physicians and Surgeons, Columbia University, New York, NY, USA.

出版信息

Cell Immunol. 2012;274(1-2):72-82. doi: 10.1016/j.cellimm.2012.02.001. Epub 2012 Feb 13.

DOI:10.1016/j.cellimm.2012.02.001

Abstract

RAGE, the multiligand receptor of the immunoglobulin superfamily of cell surface molecules, is implicated in innate and adaptive immunity. Complement component C1q serves roles in complement activation and antibody-independent opsonization. Using soluble forms of RAGE (sRAGE) and RAGE-expressing cells, we determined that RAGE is a native C1q globular domain receptor. Direct C1q-sRAGE interaction was demonstrated with surface plasmon resonance (SPR), with minimum K(d) 5.6 μM, and stronger binding affinity seen in ELISA-like experiments involving multivalent binding. Pull-down experiments suggested formation of a receptor complex of RAGE and Mac-1 to further enhance affinity for C1q. C1q induced U937 cell adhesion and phagocytosis was inhibited by antibodies to RAGE or Mac-1. These data link C1q and RAGE to the recruitment of leukocytes and phagocytosis of C1q-coated material.

摘要

RAGE 是免疫球蛋白超家族细胞表面分子的多配体受体，与先天和适应性免疫有关。补体成分 C1q 在补体激活和抗体非依赖性调理作用中发挥作用。使用 RAGE（sRAGE）的可溶性形式和表达 RAGE 的细胞，我们确定 RAGE 是天然的 C1q 球形结构域受体。表面等离子体共振（SPR）显示出直接的 C1q-sRAGE 相互作用，最低 K(d) 为 5.6 μM，在涉及多价结合的 ELISA 样实验中观察到更强的结合亲和力。下拉实验表明，RAGE 和 Mac-1 形成受体复合物，进一步增强了对 C1q 的亲和力。抗 RAGE 或 Mac-1 的抗体可抑制 C1q 诱导的 U937 细胞黏附和吞噬作用。这些数据将 C1q 和 RAGE 与白细胞募集和 C1q 包被物质的吞噬作用联系起来。