C5B-8 STEP LYSIS OF SWINE ENDOTHELIAL-CELLS BY HUMAN-COMPLEMENT AND FUNCTIONAL FEATURE OF TRANSFECTED CD59

The authors established several swine endothelial cell (SEC) lines exp ressing human CD59 by transfection of cDNA, and assessed the function of the transfectant molecules in comparison with those of membrane cof actor protein (MCP) and decay-accelerating factor (DAF) in an in vitro hyperacute rejection model of swine to human discordant xenograft. At the usual expression rate, DAF and MCP protected SEC from human compl ement mediated cell lysis, but CD59 did not block human complement att ack on SEC. However, CD59 protects SEC from cell lysis, when sufficien tly expressed as in human umbilical vein (HUVEC). The authors examined why CD59 needed so many molecules to protect human complement-mediate d SEC lysis and found that SEC underwent lysis by human C5b-8. The deg ree of C5b-8 step lysis of SEC was approximately 70% of the total acti vity (C5b-9). Additionally, CD59 protected human complement activation less efficiently at the C5b-8 step than at the C9-step. Therefore, to overcome human complement mediated SEC lysis, C8 activity must be inh ibited by dense expression of CD59.