The complement system in xenotransplantation.

The immediate barrier to xenotransplantation across phylogenetically distant species, a manifestation of natural immunity, is hyperacute rejection of the xenograft. Complement (C) plays a central pathophysiological role in hyperacute rejection. Hyperacute rejection is initiated when C is activated by natural antibodies against the vascular endothelium of the transplanted organ or by the endothelium itself. C activation fragments alone or in conjunction with natural antibodies set in motion a series of events in the vasculature of the xenogeneic organ which result in loss of endothelial functional integrity and fibrin deposition. This article reviews recent findings concerning the role of C in hyperacute rejection and evidence suggesting that inhibition of C activation may be a critical approach to avert hyperacute rejection.