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 vitro model relevant to hyperacute xenograft rejection.
Inhibition of complement activation is considered a prerequisite to overcome hyperacute xenograft rejection. In the present study, we investigated the efficacy of C1 inhibitor (C1 inh) and recombinant soluble complement receptor type 1 (rsCR1) to protect xenogeneic cells against complement-mediated cytotoxicity in an in vitro xenotransplantation model. 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 CD59 resulted in several clones where protection against complement-mediated cell destruction correlated with the expression level of the inhibitor. Addition of low concentrations of C1 inh and rsCR1 to a CD59 (human)-positive PEC clone, expressing a suboptimal level of the membrane-bound regulator, resulted in a significant improvement of protection against complement-mediated cell destruction.
Heckl-Ostreicher
B
B
Institute of Immunology, University of Heidelberg, Germany.
Wosnik
A
A
Kirschfink
M
M
D000818:Animals; D018957:CD59 Antigens / Q000494:pharmacology*; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D011951:Receptors, Complement / Q000502:physiology*; D012995:Solubility; D014183:Transplantation, Heterologous / Q000276:immunology*
D018957:CD59 Antigens; D003174:Complement C1 Inactivator Proteins; D011951:Receptors, Complement