Direct interaction between CD91 and C1q
Direct interaction between CD91 and C1q
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DOI：
10.1111/j.1742-4658.2010.07762.x
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发表时间：
2010-09-01
期刊：
影响因子：
5.4
通讯作者：
Houen, Gunnar
中科院分区：
文献类型：
--
作者：
Duus, Karen;Hansen, Erik W.;Houen, Gunnar
C1q 介导的免疫复合物和凋亡细胞清除在组织稳态和预防自身免疫性疾病中发挥着重要作用。有人认为，C1q通过CD91（α-2-巨球蛋白受体，或低密度脂蛋白受体相关蛋白）和钙网蛋白组装而成的受体复合物介导凋亡细胞的吞噬作用，其中CD91是跨膜部分，钙网蛋白作为C1q结合分子。在本研究中，我们观察到 C1q 结合来自表达 CD91 的单核细胞系的细胞以及来自人类血液的单核细胞。 C1q 与单核细胞的结合被证明与 CD91 表达相关，并且可以被 CD91 伴侣、受体相关蛋白抑制。我们还报告了显示 CD91 和 C1q 之间直接相互作用的数据。使用各种蛋白质相互作用测定来研究相互作用。通过 ELISA 和表面等离振子共振测定法观察到纯化的 C1q 和 CD91 之间的直接相互作用，其中 C1q 或 CD91 固定。这种相互作用表现出特异性，因为它是时间依赖性的、可饱和的并且可以被CD91和C1q的已知配体抑制。所得结果首次表明CD91直接识别C1q。基于这些发现，我们提出 CD91 是 C1q 的受体，并且这种多功能清道夫受体使用其配体结合位点的子集来清除 C1q 和 C1q 结合物质。
C1q-mediated removal of immune complexes and apoptotic cells plays an important role in tissue homeostasis and the prevention of autoimmune conditions. It has been suggested that C1q mediates phagocytosis of apoptotic cells through a receptor complex assembled from CD91 (alpha-2- macroglobulin receptor, or low-density lipoprotein receptor-related protein) and calreticulin, with CD91 being the transmembrane part and calreticulin acting as the C1q-binding molecule. In the present study, we observe that C1q binds cells from a CD91 expressing monocytic cell line as well as monocytes from human blood. C1q binding to monocytes was shown to be correlated with CD91 expression and could be inhibited by the CD91 chaperone, receptor-associated protein. We also report data showing a direct interaction between CD91 and C1q. The interaction was investigated using various protein interaction assays. A direct interaction between purified C1q and CD91 was observed both by ELISA and a surface plasmon resonance assay, with either C1q or CD91 immobilized. The interaction showed characteristics of specificity because it was time-dependent, saturable and could be inhibited by known ligands of both CD91 and C1q. The results obtained show for the first time that CD91 recognizes C1q directly. On the basis of these findings, we propose that CD91 is a receptor for C1q and that this multifunctional scavenger receptor uses a subset of its ligand-binding sites for clearance of C1q and C1q bound material.