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.
Dalmasso
A P
AP
Department of Laboratory Medicine and Pathology, Veterans Affairs Medical Center, Minneapolis, MN 55417.
D000818:Animals; D003167:Complement Activation; D003169:Complement Inactivator Proteins / Q000276:immunology; D003170:Complement Pathway, Alternative; D003171:Complement Pathway, Classical; D003165:Complement System Proteins / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005337:Fibrin / Q000378:metabolism; D006084:Graft Rejection; D006801:Humans; D014183:Transplantation, Heterologous
D003169:Complement Inactivator Proteins; D005337:Fibrin; D003165:Complement System Proteins