Abstract
Hyperacute rejection (HAR) of vascularized organ transplants occurs in both presensitized recipients of allografts and in discordant xenograft (Xg) recipients. HAR of allografts is currently avoided by excluding from Transplantation those patients with high levels of alloreactive antibodies, since no clinically effective treatment exists to prevent this process. These patients are then added to ever expanding waiting lists, and many die while awaiting organ Transplantation. Additionally, these lists continue to expand because of the increasing shortage of organs available for clinical Transplantation. The use of Xgs from distantly related species might relieve this problem of donor availability but is also prevented by HAR.
HAR is mediated by the binding of recipient antibodies to the endothelium of the graft, with subsequent activation of the classical pathway of complement (C). In some models, alternative pathway C activation may also play a role in this process. In an effort to prevent the C- mediated injury of HAR, our laboratory has investigated the use of soluble complement receptor type 1 (sCRl) in several animal models.
In an ACI-to-Lewis rat presensitized cardiac allograft model, the administration of sCRl significantly prolonged allograft survival in comparison to saline treated controls. In both the guinea pig-to-rat and the pig-to-cynomolgus monkey species combinations in vivo, and in an ex vivo pig-to-human model, the administration of sCR1 significantly prolonged cardiac Xg survival and function. These studies suggest that sCR1 may be a useful agent for both alloTransplantation in the presensitized recipient and xenoTransplantation.
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© 1996 Plenum Press, New York
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Pruitt, S.K., Baldwin, W.M., Bollinger, R.R., March, H.C., Sanfillippo, F. (1996). Soluble Complement Receptor and Hyperacute Rejection. In: Catravas, J.D., Callow, A.D., Ryan, U.S. (eds) Vascular Endothelium. NATO ASI Series, vol 281. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0355-8_1
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