PROTECTION OF PORCINE ENDOTHELIAL-CELLS FROM COMPLEMENT-MEDIATED CYTOTOXICITY BY THE HUMAN-COMPLEMENT REGULATORS CD59, C1 INHIBITOR, AND SOLUBLE COMPLEMENT RECEPTOR-TYPE-1 - ANALYSIS IN A PIG-TO-HUMAN IN-VITROMODEL RELEVANT TO HYPERACUTE XENOGRAFT REJECTION

Inhibition of complement activation is considered a prerequisite to ov ercome hyperacute xenograft rejection. In the present study, we invest igated the efficacy of C1 inhibitor (C1 inh) and recombinant soluble c omplement receptor type 1 (rsCR1) to protect xenogeneic cells against complement-mediated cytotoxicity in an in vitro xenotransplantation mo del. The addition of the soluble complement regulators to human serum led to a dose-dependent inhibition of complement-mediated destruction of aortic porcine endothelial cells (PEC). On a molar base, rsCR1 was more efficient than C1 inh. Transfection of PEC with cDNA of human CD5 9 resulted in several clones where protection against complement-media ted cell destruction correlated with the expression level of the inhib itor. Addition of low concentrations of C1 inh and rsCR1 to a CD59 (hu man)-positive PEC clone, expressing a suboptimal level of the membrane -bound regulator, resulted in a significant improvement of protection against complement-mediated cell destruction.