Objective: To investigate whether apoptotic cell death is involved in liver xenograft rejection and the molecular mechanism of apoptosis.
Methods: After hamster-to-rat orthotopic liver transplantation, apoptosis in the xenograft was observed histologically and by in situ end-labelling of fragmented DNA. CD8 antigen, perforin, Fas-L and TGF-β1 were observed immunohistochemically in the graft.
Results: In xenogenic rejection, OX8 (CD8) positive T lymphocyte was observed on day 2 post-transplantation, evidently on day 5. The expression of perforin and Fas-L in grafts occurred on day 4 post-transplantation, and it was more evident in the rejection. In control group,the lymphocyte was rarely seen, and the expression of Fas-L and perforin was not found. Both xenogeneic and syngeneic grafts showed the expression of TGF-β1 on the first day after transplantation. The expression of TGF-β1, however, increased subsequently in the xenogeneic graft in contrast to its normalization in the syngeneic graft. In the xenogeneic graft, apoptosis occurred on day 1 after transplantation, decreased on day 2, increased on day 3, and peaked on day 5. Apoptosis was similar in the syngeneic and xenogeneic grafts on day 1 after transplantation, but decreased to normal one day later. The more severe apoptosis, the more severe acute rejection, and the more evident expression of perforin, Fas-L and TGF-β1.
Conclusion: Apoptosis as a mechanism of cell death exists in the acute rejection of liver xenograft, and it is related closely to the expression of perforin, TGF-β1 and Fas-L.