EFFECTS OF TRANSFECTED COMPLEMENT REGULATORY PROTEINS, MCP, DAF, AND MCP DAF HYBRID, ON COMPLEMENT-MEDIATED SWINE ENDOTHELIAL-CELL LYSIS/

We established several swine endothelial cell (SEC) lines, expressing human MCP (CD46), DAF (CD55), and MCP/DAF hybrid by transfection of cD NA, and assessed the function of these transfectant molecules on compl ement-mediated cell lysis as an in vitro hyperacute rejection model of swine to human discordant xenograft. Discordant organ xenografts are hyperacutely rejected by complement activation. Amelioration of comple ment-mediated lysis by these transfectant molecules was tested in each SEC line by lactate dehydrogenase assay. Naive swine endothelial cell s were markedly damaged by human complement mainly via the classical p athway, activating only minimally the alternative pathway of human com plement. Both MCP and DAF protected SEC from human complement attack i n parallel with the expression density, with DAF being more effective than MCP. The MCP/DAF hybrid was more effective than MCP alone, and as effective as DAF in this system. The results suggest that the transfe ction of DAF or the MCP/DAF hybrid cDNA into organs to be transplanted could protect against hyperacute rejection.