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Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1991 Oct;86(Suppl 1):31–35.

Reaction of complement with endothelial cells in a model of xenotransplantation.

A P Dalmasso 1, J L Platt 1, F H Bach 1
PMCID: PMC1554041  PMID: 1718641

Abstract

We review our studies on the role of complement (C) as mediator of xenograft hyperacute rejection using an in vitro model consisting of porcine endothelial cells as target and human serum as source of natural antibodies and C. Cytotoxicity of endothelial cells required IgM antibodies to porcine endothelial cells, and the classical pathway and membrane attack complex of C. These findings correlated with in vivo results of porcine organs transplanted into rhesus monkeys, which showed a) co-deposition of IgM, C3, C4 and C9, along blood vessels of rejecting organs, with trace deposits of factors B or P, and b) minimal deposition of IgM and C components in transplants with prolonged survival that were performed in rhesus monkeys depleted of natural antibodies but with normal C levels. Human serum causes activation of porcine endothelial cells manifested by release of heparan sulfate proteoglycan. Heparan sulfate release was induced by C5a alone. A new approach to avert xenograft hyperacute rejection was tested. To inhibit cytotoxicity of porcine endothelial cells by human C, the membrane-associated C inhibitor decay-accelerating factor (DAF) of human origin was incorporated into endothelial cells. Human DAF was able to efficiently inhibit C-mediated killing of porcine endothelial cells, suggesting that the use of DAF and other C inhibitors could be used to interfere with C-mediated xenograft hyperacute rejection.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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