High-level endothelial expression of human CD59 prolongs heart function in an ex vivo model of xenograft rejection

被引:28
作者
Cowan, PJ [1 ]
Somerville, CA [1 ]
Shinkel, TA [1 ]
Katerelos, M [1 ]
Aminian, A [1 ]
Romanella, M [1 ]
Tange, MJ [1 ]
Pearse, MJ [1 ]
D'Apice, AJF [1 ]
机构
[1] St Vincents Hosp, Immunol Res Ctr, Fitzroy, Vic 3065, Australia
关键词
D O I
10.1097/00007890-199803270-00010
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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收藏
页码:826 / 831
页数:6
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