Regulation of complement classical pathway by association of C4b-binding protein to the surfaces of SK-OV-3 and caov-3 ovarian adenocarcinoma cells
Regulation of complement classical pathway by association of C4b-binding protein to the surfaces of SK-OV-3 and caov-3 ovarian adenocarcinoma cells
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DOI：
10.4049/jimmunol.167.2.935
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发表时间：
2001-07-15
影响因子：
4.4
通讯作者：
Meri, S
中科院分区：
文献类型：
--
作者：
Holmberg, MT;Blom, AM;Meri, S
补体的液相调节剂的作用是抑制补体的过度激活和维持血液中的稳态。通过结合和灭活细胞表面的补体成分，它们还可以保护自体细胞免受补体介导的细胞毒性和吞噬作用。在这项研究中，我们想要发现c4b结合蛋白（C4bp），一个经典补体途径的液相调节剂，是否可以以功能活性的形式直接结合到细胞表面。通过对几种恶性细胞系的筛选，我们发现卵巢腺癌细胞SK-OV-3、Caov-3和SW626能够结合C4bp。与重组缺失突变体的结合试验表明，C4bp的主要结合位点位于α链补体控制蛋白4结构域。功能测试表明，肿瘤细胞结合的C4bp保留了对因子i介导的CO失活的辅助因子活性，从而增加了对这些细胞表面经典补体途径激活的控制。这些结果证明了补体调控细胞表面，特别是卵巢恶性肿瘤细胞表面的新机制。
The role of fluid-phase regulators of complement is to inhibit excessive complement activation and maintain homeostasis in blood. By binding to and inactivating complement components on cell surfaces, they can also protect autologous cells from complement-mediated cytotoxicity and phagocytosis. In this study, we wanted to find out whether C4b-binding protein (C4bp), a fluid-phase regulator of the classical complement pathway, could directly bind to cell surfaces in a functionally active form. After screening several malignant cell lines, we observed that the ovarian adenocarcinoma cell lines SK-OV-3, Caov-3, and SW626 were capable of binding C4bp. Binding tests with recombinant deletion mutants suggested that the primary binding site on C4bp is located on the alpha -chain complement control protein 4 domain. Functional tests showed that tumor cell-bound C4bp retained its cofactor activity for factor I-mediated inactivation of CO, thus increasing the control of classical complement pathway activation on the surfaces of these cells. These results demonstrate a novel mechanism of complement regulation on cell surfaces, particularly on those of malignant ovarian tumor cells.