PROTECTION FROM COMPLEMENT-MEDIATED INJURY IN LIVERS AND KIDNEYS OF TRANSGENIC MICE EXPRESSING HUMAN-COMPLEMENT REGULATORS

The major problem in the use of phylogenetically distant donors is a f ast, strong reaction called hyperacute rejection. This reaction mediat ed by complement is directed against the vascular endothelia of the tr ansplanted organ. Complement activation is tightly controlled by sever al regulatory proteins which inhibit the formation and function of dif ferent complement components. To verify the hypothesis that organs exp ressing such inhibitory factors could be spared from complement-mediat ed hyperacute rejection, we have generated mice transgenic for the hum an complement inhibitor membrane cofactor protein (hMCP) and decay acc elerating factor (hDAF). Different levels of hMCP and/or hDAF expressi on, according to the promoter used, were detected by RNA analysis in t he major organs, specifically on the organ vascular endothelia, as rev ealed by immunohistochemical analysis. The development of an in vivo m odel of human plasma perfusion allowed the characterization of complem ent-mediated damage in control animals and the degree of protection du e to the presence of hMCP, hDAF, or both in the organs derived from si ngle or double transgenic mice. In this paper we compare the level of expression of complement regulators with the degree of protection in t wo major organs: liver and kidney.