Protection of xenogeneic cells from human complement-mediated lysis by the expression of human DAF, CD59 and MCP

Protection of xenogeneic cells from human complement-mediated lysis by the expression of human DAF, CD59 and MCP
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DOI:
10.1111/j.1574-695x.2001.tb00521.x
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发表时间:
2001-10-01
影响因子:
--
通讯作者:
Cai, CC
Cai, CC
中科院分区:
其他
文献类型:
--
作者:
Huang, J;Gou, DM;Cai, CC

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CD 59和膜辅因子蛋白(MCP,CD 46)是广泛表达的细胞表面糖蛋白,其保护宿主细胞免受同源补体攻击的影响。将从中国人胚胎中克隆的编码人CD 59和MCP的cDNA分别转染NHI 3 T3细胞,使细胞表面表达人CD 59和MCP蛋白。研究了表达蛋白的功能特性。当转染的细胞暴露于人血清作为补体和天然存在的抗小鼠抗体的来源时,它们对人补体介导的细胞杀伤具有抗性。然而,细胞仍然对兔和豚鼠补体敏感。人CD 59和MCP只能保护NIH/3 T3细胞免受人补体介导的裂解。这些结果表明,这些蛋白质的补体抑制活性是物种选择性的。将CD 59和MCP的eDNAs分别转染入转人CD 49基因的猪的内皮细胞(EC)中,以研究推定的协同作用。与仅表达MCP蛋白的细胞相比,表达MCP蛋白和MCP蛋白或表达CD 59蛋白和CD 59蛋白的EC表现出更好的抗人血清细胞溶解的保护作用。(C)2001年,欧洲微生物学会联合会。出版社:Elsevier Science BN All rights reserved.
CD59 and membrane cofactor protein (MCP, CD46) are widely expressed cell surface glycoproteins that protect host cells from the effect of homologous complement attack. cDNAs encoding human CD59 and MCP cloned from Chinese human embryo were separately transfected into NHI3T3 cells resulting in the expression of human CD59 and MCP protein on the cell surface. The functional properties of expressed proteins were studied. When the transfected cells were exposed to human serum as a source of complement and naturally occurring anti-mouse antibody, they were resistant to human complement-mediated cell killing. However, the cells remained sensitive to rabbit and guinea pig complement. Human CD59 and MCP can only protect NIH/3T3 cells from human complement-mediated lysis. These results demonstrated that complement inhibitory activity of these proteins is species-selective. The eDNAs of CD59 and MCP were also separately transfected into the endothelial cells (ECs) of the pigs transgenic for the human DAF gene to investigate a putative synergistic action. The ECs expressing both DAF and MCP proteins or both DAF and CD59 proteins exhibited more protection against cytolysis by human serum compared to the cells with only DAF expressed alone. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science BN. All rights reserved.