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

Transplantation
P J CowanA J d'Apice

Abstract

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. The level of expression of CD59 in two lines of transgenic mice, in which CD59 is expressed under the control of either the murine H2Kb (MHC class I) promoter (line CA-17) or the endothelium-specific human intercellular adhesion molecule-2 promoter (line 237-7), was compared by immunohistochemistry and flow cytometry. Hearts from both groups and wild-type controls were perfused ex vivo with human plasma, and mean heart work for each group was compared over a 60-min period. 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 i...Continue Reading

References

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Citations

Mar 20, 1999·Transplantation Proceedings·J M GrinyoJ Torras
Aug 14, 2003·Molecular Immunology·Daniel Turnberg, Marina Botto
May 9, 2009·Transplantation·Adam D GriesemerKazuhiko Yamada
Dec 16, 1998·Xenotransplantation·M Koulmanda, H Auchincloss
Dec 4, 2010·Transplantation Reviews·Hilton GockPeter Cowan
Apr 16, 2005·Clinical Microbiology Reviews·Alain L Servin

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