Analysis of the Fas system and Bcl-2 in rat liver allograft rejection.
BACKGROUND
Apoptosis is involved in the mechanism of cell death observed in 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. We used rat models to investigate the expression of Fas/Fas ligand and apoptosis-related proteins during liver allograft rejection.


METHODS
DA rats to Lewis, and Lewis to Lewis orthotopic liver transplantation were performed; liver samples were collected on days 1, 3, 5, 7, and 9 postoperatively (each n = 3). Apoptosis was monitored by TUNEL and electron microscopy. The expression of Fas, FasL, bcl-2, and bax 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 bax mRNA were constitutively expressed in both of the groups. The expression of Fas ligand mRNA 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 expressed in the isografts while it decreased in the allografts. The immunohistochemical 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 regulatory factors of apoptosis, such as bcl-2, might also be involved in this pathogenesis.
Hiroyasu
S
S
The First Department of Surgery, University of the Ryukyus, School of Medicine, Okinawa, 903-0125, Japan.
Shiraishi
M
M
Koji
T
T
Mamadi
T
T
Sugawa
H
H
Muto
Y
Y
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053222:Fas Ligand Protein; D006084:Graft Rejection / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D014184:Transplantation, Homologous; D051028:bcl-2-Associated X Protein; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
C494828:Bax protein, rat; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D019014:fas Receptor