High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection
High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection
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DOI：
10.1097/00007890-199803270-00010
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发表时间：
1998-03-27
期刊：
影响因子：
6.2
通讯作者：
D'Apice, AJF
中科院分区：
文献类型：
--
作者：
Cowan, PJ;Somerville, CA;D'Apice, AJF
背景。不一致异种移植物的超急性排斥依赖于受体补体系统的激活，在供体组织中转基因表达受体补体调节因子已被证明是处理超急性排斥反应的有前途的方法，尽管补体调节因子表达水平与保护程度之间的关系尚未明确。在这里，我们在异种移植排斥的离体模型中使用 CD59 转基因小鼠心脏检查这种关系。方法，通过免疫组织化学和流式细胞仪比较两系转基因小鼠中 CD59 的表达水平，其中 CD59 在鼠 H2K（b）（MHC I 类）启动子（系 CA-17）或内皮特异性人细胞间粘附分子启动子（系 237-7）的控制下表达。细胞计数术。两组和野生型对照的心脏均用人血浆离体灌注，并在 60 分钟内比较每组的平均心脏做功。结果，从纯合子 CA-17 小鼠中分离的心脏内皮细胞上的 CD59 表达比从杂合子 237-7 小鼠中分离的心脏内皮细胞上低 25 至 30 倍，用 6% 人血浆灌注的 CA-17 心脏表现出膜攻击沉积的减少与非转基因小鼠心脏相比，237-7心脏表现出复杂的功能，但不是功能的延长，相反，237-7心脏在用20%血浆灌注期间显示出显着的功能延长。结论，CD59的高水平内皮特异性表达可有效延长用20%人血浆灌注的小鼠心脏的功能，而低水平、更广泛的表达不能提供免受6%血浆的保护。
Background. Hyperacute rejection of discordant xenografts is dependent on activation of the complement system of the recipient, Transgenic expression of recipient complement regulatory factors in donor tissue has proved to be a promising approach to dealing with hyperacute rejection, although the relationship between the level of complement regulatory factor expression and the degree of protection is not well established. Here, we examine this relationship using CD59 transgenic mouse hearts in an ex vivo model of xenograft rejection,Methods, The level of expression of CD59 in two lines of transgenic mice, in which CD59 is expressed under the control of either the murine H2K(b) (MHC class I) promoter (line CA-17) or the endothelium-specific human intercellular adhesion molecule-a promoter (line 237-7), was compared by immunohistochemistry and flow cytometry. Hearts from both groups and wildtype controls were perfused ex vivo with human plasma, and mean heart work for each group was compared over a 60-min period,Results, CD59 expression on cardiac endothelial cells isolated from homozygous CA-17 mice was 25- to 30-fold lower than that on cardiac endothelial cells from heterozygous 237-7 mice, CA-17 hearts perfused with 6% human plasma exhibited a reduction in deposition of the membrane attack complex, but not a prolongation of function, compared with nontransgenic mouse hearts, In contrast, 237-7 hearts showed significantly prolonged function during perfusion with 20% plasma,Conclusions, High-level endothelial-specific expression of CD59 was effective in prolonging the function of mouse hearts perfused with 20% human plasma, whereas low-level, broader expression did not provide protection from 6% plasma.