PROTECTION OF XENOGENEIC CARDIAC ENDOTHELIUM FROM HUMAN-COMPLEMENT BYEXPRESSION OF CD59 OR DAF IN TRANSGENIC MICE

We investigated the ability of membrane-bound human complement regulat ory proteins to control complement-driven humoral immune reactions on murine microvasculature. The human complement regulatory proteins CD59 and DAF were expressed using heterologous promoters in a variety of t issues in transgenic mice. Animals expressing these gene products are healthy and exhibit significant levels of endothelial cell expression of CD59 and DAF in cardiac muscle. Transgenic hearts perfused with hum an plasma exhibited profound reductions in the level of complement dep osition compared with nontransgenic controls. We have also produced tr ansgenic pigs that express these two human genes. Our results indicate that expression of complement regulatory proteins can control activat ion of complement and suggest that these proteins may have therapeutic applications in some inflammatory diseases and in the development of xenogeneic organs for human transplantation.