Popis: |
The immediate and devastating effects of hyperacute rejection in xenotransplantation have tended to focus research and therapeutic strategies on this major hurdle, and there is no question that without such strategies the problems facing xenotransplantation cannot even be studied experimentally [1]. Nevertheless, if xenotransplantation is to become a clinical alternative, it will be necessary to confront the full spectrum of pathophysiological mechanisms at play. Many of these are well known clinically in the context of allotransplantation [2]. In xenotransplantation, the most critical steps are the immediate deposition of xenoreac-tive natural antibodies on graft endothelium causing complement activation, the activation of coagulation and thrombotic mechanisms, the intermediate inflammatory and immune cellular responses, and the anticipated longer-term processes of tissue hyperplasia and remodeling. Many of the cellular and molecular culprits driving or amplifying these pathways are known and inextricably linked: others yet to be discovered or fully understood will have to be woven into the existing tapestry. |