Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism.

Membrane cofactor protein (CD46) protects cells from complement-mediated attack by an intrinsic mechanism.
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DOI:
10.1084/jem.175.6.1547
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发表时间:
1992-06-01
期刊:
The Journal of experimental medicine
影响因子:
--
通讯作者:
Atkinson JP
Atkinson JP
中科院分区:
其他
文献类型:
--
作者:
Oglesby TJ;Allen CJ;Liszewski MK;White DJ;Atkinson JP

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C3的切割是补体(C)激活的一个关键步骤,在经典和替代途径。该反应受C活化蛋白家族调节因子控制。膜辅助因子蛋白(MCP)是因子i介导的C3b和C4b失活的辅助因子。MCP作为一种广泛分布的膜蛋白,可以保护宿主细胞免受C的无意激活。人MCP最近被证明可以保护转染的啮齿动物细胞免受人c介导的裂解。在本报告中,我们使用转染人MCP并暴露于人血清作为C和天然抗小鼠抗体来源的NIH/3T3细胞,研究了MCP表达与C3b沉积和细胞保护的关系。MCP以剂量依赖性的方式抑制C3b沉积,并抑制表达C3b的小鼠细胞的裂解。MCP对旁观细胞的裂解没有抑制作用。这些结果表明MCP的保护作用,在细胞水平上,通过内在机制。
The cleavage of C3 is a critical step for complement (C) activation in the classical and alternative pathways. This reaction is controlled by the regulators of C activation protein family. Membrane cofactor protein (MCP) is a cofactor for the factor I-mediated inactivation of C3b and C4b. As a widely distributed membrane protein, MCP may protect host cells from inadvertent C activation. Human MCP has recently been shown to protect transfected rodent cells from human C-mediated lysis. In this report the relationship of MCP expression to C3b deposition and cytoprotection was examined using NIH/3T3 cells transfected with human MCP and exposed to human serum as a source of C and naturally occurring anti-mouse antibody. MCP inhibited C3b deposition in a dose-dependent fashion and inhibited lysis of the mouse cells expressing it. MCP did not inhibit lysis on bystander cells. These results demonstrate the protective role of MCP, at the cellular level, by an intrinsic mechanism.
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