ROLE OF ENDOTHELIAL-CELLS IN TRANSPLANTATION

Endothelial cell activation with accompanying vascular inflammatory ch anges is considered central to the experimental manifestations of both hyperacute and delayed xenograft rejection responses. Natural xenorea ctive antibodies directed at alpha-galactosyl residues of xenogeneic g lycoproteins and glycolipids, with associated complement activation vi a the classical pathway, are considered major immediate mediators of g raft endothelial cell injury in the clinically relevant discordant swi ne to primate combinations. In delayed xenograft rejection processes, where recipients are treated prophylactically to ameliorate these init ial events, activation of infiltrating mononuclear phagocytes and natu ral killer cells are associated with ongoing endothelial cell activati on processes, procoagulant generation and vascular thrombosis. Allogra ft hyperacute rejection is observed when vascularised organs are trans planted to sensitized individuals with high levels of cytotoxic antibo dies. Less dramatic forms of humoral allograft rejection (termed accel erated or vascular rejection) and the more common cell-mediated endoth elialitis are associated with significant graft damage. Endothelial ce ll activation is also linked with graft preservation injury, forms of chronic rejection and delayed graft loss. Experimental work is current ly being directed at the control of hyperacute rejection, the close un derstanding of endothelial cell thromboregulation in both transplanted xeno- and allografts and the development of novel therapeutic agents including gene therapy and the possible use of organs from transgenic animals.