Analysis of the Fas system and bcl-2 in rat liver allograft rejection

Background. Apoptosis is involved in the mechanism of cell death observed i n liver allograft rejection. The liver cells are sensitive to Fas-mediated apoptosis; however, little is known about the involvement of the Fas system in liver allograft rejection. are used rat models to investigate the expre ssion of Fas/Fas ligand and apoptosis-related proteins during liver allogra ft rejection. Materials and methods. DA rats to Lewis, and Lewis to Lewis orthotopic live r transplantation were performed; liver samples were collected on days 1, 3 , 5, 7, and 9 postoperatively (each n = 3). Apoptosis was monitored by TUNE L and electron microscopy. The expression of Fas, Fast, bcl-2, and bar was examined at the mRNA level and by means of immunohistochemistry. Results. The TUNEL index in the allografts and isografts on day 7 was 20.1 +/- 1.5 and 7.7 +/- 2.6/1000 cells, respectively. Fas and bar mRNA were con stitutively expressed in both of the groups. The expression of Fas ligand m RNA in the allografts which rose on day 5 was 10 times stronger compared to that in the isografts. On the other hand, bcl-2 mRNA was generally express ed in the isografts while it decreased in the allografts. The immunohistoch emical analysis also showed an increased reactivity of Fas ligand on day 5 in the allograft, which was observed both in parenchymal and nonparenchymal cells. Conclusions. These results strongly suggest that Fas/Fas ligand interaction mediates the liver injury during allograft rejection. In addition, other r egulatory factors of apoptosis, such as bcl-2, might also be involved in th is pathogenesis. (C) 1999 Academic Press.