Protection of porcine endothelial cells from complement-mediated cytotoxicity by the human complement regulators CD59, C1 inhibitor, and soluble complement receptor type 1 - Analysis in a pig-to-human in vitro model relevant to hyperacute xenograft rejection
Protection of porcine endothelial cells from complement-mediated cytotoxicity by the human complement regulators CD59, C1 inhibitor, and soluble complement receptor type 1 - Analysis in a pig-to-human in vitro model relevant to hyperacute xenograft rejection
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DOI：
10.1097/00007890-199612150-00032
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发表时间：
1996-12-15
期刊：
影响因子：
6.2
通讯作者：
Kirschfink, M
中科院分区：
文献类型：
--
作者：
HecklOstreicher, B;Wosnik, A;Kirschfink, M
抑制补体活化被认为是克服超急性异种移植排斥反应的先决条件。在本研究中，我们在体外异种移植模型中研究了C1抑制剂（C1 inh）和重组可溶性补体受体1型（rsCR1）保护异种细胞免受补体介导的细胞毒性的功效。在人血清中添加可溶性补体调节剂可导致补体介导的猪主动脉内皮细胞（PEC）破坏的剂量依赖性抑制。在摩尔碱中，rsCR1的效率高于C1。转染人CD59 cDNA的PEC产生了几个克隆，其中对补体介导的细胞破坏的保护与抑制剂的表达水平相关。将低浓度的C1 inh和rsCR1添加到CD59（人）阳性的PEC克隆中，表达亚理想水平的膜结合调节因子，导致对补体介导的细胞破坏的保护显著提高。
Inhibition of complement activation is considered a prerequisite to overcome hyperacute xenograft rejection. In the present study, we investigated the efficacy of C1 inhibitor (C1 inh) and recombinant soluble complement receptor type 1 (rsCR1) to protect xenogeneic cells against complement-mediated cytotoxicity in an in vitro xenotransplantation model. The addition of the soluble complement regulators to human serum led to a dose-dependent inhibition of complement-mediated destruction of aortic porcine endothelial cells (PEC). On a molar base, rsCR1 was more efficient than C1 inh. Transfection of PEC with cDNA of human CD59 resulted in several clones where protection against complement-mediated cell destruction correlated with the expression level of the inhibitor. Addition of low concentrations of C1 inh and rsCR1 to a CD59 (human)-positive PEC clone, expressing a suboptimal level of the membrane-bound regulator, resulted in a significant improvement of protection against complement-mediated cell destruction.