Mikata S, Miyagawa S, Yoshitatsu M, Ikawa M, Okabe M, Matsuda H, Shirakura R
Division of Organ Transplantation, Osaka University, Suita, Japan.
Transpl Immunol. 1998 Jun;6(2):107-10. doi: 10.1016/s0966-3274(98)80025-7.
Complement receptor type 1 (CR1, CD35) contains both factor I cofactor activity and convertase decay accelerating activity, but is, in general, thought to be an extrinsic regulator of complement activation. In this study, we prepared a phosphatidylinositol (PI)-anchored mini-CR1, which is composed of the short consensus repeat (SCR) 8-11 of CR1 and the PI anchor of DAF, and expressed it stably on a swine endothelial cell (SEC) line. We then examined the intrinsic regulatory activity of the mini-CR1, with respect to complement-mediated cell lysis as an in vitro hyperacute rejection model of a swine to human discordant xenograft. Flowcytometric profiles of the stable SEC lines with mini-CR1 showed a moderate level of expression for this molecule. Mini-CR1 blocked human complement-mediated cell lysis by approximately 50-70% on SEC. From the data of this study and our previous studies, mini-CR1 was more effective than membrane cofactor protein (MCP, CD46), and as effective as decay accelerating factor (DAF, CD55) in this system. The results suggest that PI-anchored mini-CR1 represents a useful molecule for clinical xenotransplantation.
1型补体受体（CR1，CD35）兼具I因子辅因子活性和转化酶衰变加速活性，但一般被认为是补体激活的外在调节因子。在本研究中，我们制备了一种磷脂酰肌醇（PI）锚定的微型CR1，它由CR1的短共识重复序列（SCR）8-11和衰变加速因子（DAF）的PI锚组成，并在猪内皮细胞（SEC）系中稳定表达。然后，作为猪与人不匹配异种移植的体外超急性排斥模型，我们研究了微型CR1对补体介导的细胞裂解的内在调节活性。带有微型CR1的稳定SEC系的流式细胞术分析显示该分子有中等水平的表达。微型CR1在SEC上可使人类补体介导的细胞裂解阻断约50%-70%。根据本研究及我们之前研究的数据，在该系统中，微型CR1比膜辅因子蛋白（MCP，CD46）更有效，且与衰变加速因子（DAF，CD55）效果相当。结果表明，PI锚定的微型CR1是临床异种移植中一种有用的分子。
