HIGH-LEVEL COEXPRESSION OF COMPLEMENT REGULATORS ON VASCULAR ENDOTHELIUM IN TRANSGENIC MICE - CD55 AND CD59 PROVIDE GREATER PROTECTION FROMHUMAN COMPLEMENT-MEDIATED INJURY THAN CD59 ALONE

High-level endothelial expression of the human complement regulatory f actor CD59 has been shown to protect transgenic mouse hearts from huma n complement-mediated injury in an ex vivo perfusion model. In this st udy we examine whether co-expression of CD55 provides additional prote ction. CD55/CD59 double-transgenic mice were generated by co-injection of CD55 and CD59 expression constructs driven by the human intercellu lar adhesion molecule 2 (ICAM-2) promoter. A line was established from one mouse that exhibited strong expression of CD55 and CD59 on vascul ar endothelium in the heart and other transplantable organs. An ex viv o perfusion model was used to compare hearts from these CD55/CD59 mice with hearts from a previously established line, which expressed CD59 at a similar level to the double transgenic line, CD59 hearts displaye d prolonged survival compared to wild-type hearts during perfusion wit h 40% human plasma and maintained approximately 20% maximum work after 60 min. CD55/CD59 hearts were further protected, with work maintained at 35% of the maximum level after 60 min. The data demonstrate that h igh-level endothelial co-expression of CD55 and CD59 provides greater protection from human complement-mediated injury in this model than ex pression of CD59 alone.