A surface-bound form of human C1 esterase inhibitor improves xenograft rejection.
A surface-bound form of human C1 esterase inhibitor improves xenograft rejection.
复制标题
表面结合形式的人 C1 酯酶抑制剂可改善异种移植排斥。
DOI：
10.1097/00007890-200003150-00013
复制
发表时间：
2000
期刊：
影响因子：
6.2
通讯作者：
R. Shirakura
中科院分区：
文献类型：
--
作者：
K. Matsunami;S. Miyagawa;M. Yamada;M. Yoshitatsu;R. Shirakura
背景
本研究的目的是研究 C1 酯酶抑制剂 (C1-INH) 分子对抗人补体攻击猪内皮细胞 (SEC) 膜的作用。人 C1-INH 在液相经典途径的第一步中充当补体反应的抑制剂。
方法
构建了由 C1-INH 全长编码序列和衰变加速因子 (CD55) 的糖基磷脂酰肌醇 (GPI) 锚组成的表面结合形式的人 C1-INH (C1-INH-PI)，然后通过转染构建的 cDNA 制备表达 C1-INH-PI 的稳定中国仓鼠卵巢肿瘤 (CHO) 细胞系和 SEC 细胞系。为了方便起见，使用 CHO 转染子研究了异种表面上转染分子的基本功能。然后，作为猪与人不一致异种移植物的体外超急性排斥模型，评估了 C1-INH 介导的 SEC 免受人补体影响的功效。
结果
具有 C1-INH-PI 的稳定 CHO 和 SEC 转染子的流式细胞分析显示这些分子具有中等水平的表达。磷脂酰肌醇特异性磷脂酶 C (PI-PLC) 处理后，C1-INH 水平显着降低，表明该分子以 PI-锚定形式存在。大约 51.3 x 10(4) 和 13.3 x 10(4) 分子的 C1-INH-PI 分别在 CHO 细胞上阻断人补体介导的细胞裂解约 75%，在 SEC 细胞上阻断人补体介导的细胞裂解 60-65%。此外，人C1-INH分子的补体抑制活性不受同源限制。
结论
结果表明，C1-INH 的表面结合形式是防止异种移植物超急性排斥反应的良好候选者。
BACKGROUND
The purpose of the present study was to investigate the effect of the C1 esterase inhibitor (C1-INH) molecule against human complement attack on a swine endothelial cell (SEC) membrane. Human C1-INH functions as an inhibitor for complement reaction in the first step of the classical pathway in the fluid phase.
METHODS
A surface-bound form of human C1-INH (C1-INH-PI) consisting of a full-length coding sequence of C1-INH and a glycosylphosphatidylinositol (GPI) anchor of the decay-accelerating factor (CD55) was constructed, and stable Chinese hamster ovarian tumor (CHO) cell lines and SEC lines expressing C1-INH-PI were then prepared by transfection of the constructed cDNA. The basic function of the transfected molecules on the xenosurface was investigated using CHO transfectants for the sake of convenience. The efficacy of C1-INH-mediated protection of SEC from human complement was then assessed as an in vitro hyperacute rejection model of a swine-to-human discordant xenograft.
RESULTS
Flowcytometric profiles of the stable CHO and SEC transfectants with C1-INH-PI showed a medium level of expression of these molecules. The C1-INH levels were significantly reduced as a result of phosphatidylinositol-specific phospholipase C (PI-PLC) treatment, suggesting that the molecules were present as the PI-anchor form. Approximately 51.3 x 10(4) and 13.3 x 10(4) molecules of C1-INH-PI blocked human complement-mediated cell lysis by approximately 75% on the CHO cell and by 60-65% on the SEC cell, respectively. In addition, the complement-inhibiting activity of human C1-INH molecules is not homologously restricted.
CONCLUSIONS
The results suggest that the surface-bound form of C1-INH represents a good candidate as a safeguard against hyperacute rejection of xenografts.
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影响因子：
2.2
作者：
KORZENIEWSKI, C;CALLEWAERT, DM
通讯作者：
CALLEWAERT, DM
影响因子：
2.9
作者：
BOCK, SC;SKRIVER, K;MAGNUSSON, S
通讯作者：
MAGNUSSON, S
DOI：
10.1073/pnas.91.23.11153
发表时间：
1994-11-08
影响因子：
11.1
作者：
FODOR, WL;WILLIAMS, BL;SQUINTO, SP
通讯作者：
SQUINTO, SP
组胺、补体和黄嘌呤氧化酶在皮肤热损伤中的作用。
DOI：
--
发表时间：
1989
期刊：
The American journal of pathology
影响因子：
--
作者：
Friedl,HP;Till,GO;Trentz,O;Ward,PA
通讯作者：
Ward,PA