COMPLEMENT AND XENOTRANSPLANTATION - STRATEGIES OF THERAPEUTIC INTERVENTION

Hyperacute graft rejection triggered by the activation of the recipien t's complement system represents the major obstacle to successful xeno transplantation. After the binding of preformed antibodies to vascular glycoproteins complement-induced activation and injury of endothelial cells with subsequent thrombosis leads to rapid destruction of foreig n tissues. Inhibition of complement activation is therefore considered as a prerequisite for xenograft survival. Recent animal and cell cult ure experiments suggest that support of the physiological regulation o f the complement system appears to be most promising. Besides the appl ication of soluble complement inhibitors (e.g. soluble complement rece ptor 1, sCR1; C1 inhibitor) the genetic transfer of human membrane-bou nd complement regulatory proteins (e.g. DAF, CD59) offers new chances to protect the xenograft against the cytolytic complement attack. Resu lts from the authors' experiments shall be included in a short overvie w to the issue.