Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage
Transgenic pigs expressing human CD59 and decay-accelerating factor produce an intrinsic barrier to complement-mediated damage
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DOI：
10.1097/00007890-199701150-00027
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发表时间：
1997-01-15
期刊：
影响因子：
6.2
通讯作者：
Logan, JS
中科院分区：
文献类型：
--
作者：
Byrne, G;McCurry, KR;Logan, JS
我们鉴定了一种表达人类补体调节蛋白人类CD59和人类衰变加速因子的转基因猪。这些基因在异源启动子的控制下，在各种器官中表达，包括心脏、肾脏和肝脏的血管系统。我们证明，适度水平的这些基因产物足以保护外周血细胞免受人类或狒狒补体的影响。在猪到狒狒异位心脏移植中，我们发现这些蛋白的表达足以阻断补体介导的损伤，而补体介导的损伤是这种异种移植的标志。这些结果表明，当使用非转基因器官时，内在补体调节蛋白功能具有显著的物种特异性，这种特异性在转基因器官中表现得很明显，其中低水平的人CD59和人去趋化因子的表达显著影响了导致异种移植排斥的体液免疫反应。这一结果表明，高水平的人类补体调节蛋白表达的转基因器官将足以缓解目前阻碍异种器官用于人类移植的体液免疫屏障。
We characterize a line of transgenic pigs that express the human complement-regulatory proteins human CD59 and human decay-accelerating factor. These genes, under the control of heterologous promoters, are expressed in a variety of organs, including the vasculature of the heart, kidney, and liver. We demonstrate that moderate levels of these gene products are sufficient to protect peripheral blood cells from human or baboon complement. Using pig to baboon heterotopic heart transplants, we show that expression of these proteins is sufficient to block the complement-mediated damage that is the hallmark of such xenografts, when nontransgenic organs are used, These results indicate that there is significant species specificity of intrinsic complement regulatory protein function, This specificity is evident in transgenic organs in which low levels of human CD59 and human decey-accelerating factor expression significantly effect the humoral immune response that causes xenograft rejection, This result suggests that transgenic organs with high levels of human complement-regulatory protein expression will be sufficient to alleviate the humoral immunological barriers that currently block the use of xenogeneic organs for human transplantation.