APOPTOSIS IS INVOLVED IN ACUTE CARDIAC ALLOGRAFT-REJECTION IN RATS

Background. Allograft rejection remains a major obstacle to long-term survival in heart transplantation. Recent studies have demonstrated th at apoptotic cell death may occur in acute allograft rejection. The pu rpose of this study was to determine whether apoptotic cell death is i nvolved in rat cardiac allograft rejection through both the perforin/g ranzyme pathway and the Fas/Fas ligand (Fas-L) pathway. Methods. Group s of Lewis (RT1(1)) rats underwent heterotopic heart transplantation f rom disparate DA (RT1(a)) or syngeneic Lewis rats. The cardiac grafts were harvested 1, 3, or 5 days after transplantation and analyzed for apoptotic cell death using DNA nick-end labeling, immunocytochemistry, and electron microscopy. In addition, the expression of granzyme B, p erforin, pas, and Fas-L messenger RNA were analyzed by reverse transcr iptase-polymerase chain reaction. Results. Apoptotic cell death of car diac myocytes was prominent in allografts on day 5 after transplantati on. Fas gene transcripts were constitutively expressed in both syngene ic and allogeneic grafts, whereas expression of Fas-L, was only upregu lated in allografts with ongoing rejection. Granzyme B and perforin ge ne expression were also upregulated in allografts with ongoing rejecti on. Conclusions. These results suggest that myocyte apoptosis through both the perforin-granzyme pathway and the Fas-Fas-L pathway may be in volved in cardiac allograft rejection in rats. (C) 1998 by The Society of Thoracic Surgeons.