Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival.
BACKGROUND
Expression of Fas ligand (FasL) on the graft by gene transduction is expected to introduce apoptosis to lymphocytes to protect rejection, but the FasL-expressing graft cells may also induce apoptosis as the graft usually expresses Fas antigens. In this study, a strong antiapoptotic gene, bcl-2, was cotransfected with the FasL gene in rat liver graft to protect against Fas-mediated cell death and to prolong recipient survival.


METHODS
Orthotopic liver transplantation was done in a strain combination of DA to LEW rats. After donor vascular isolation, adenovirus-mediated FasL and bcl-2 genes were cotransfected in the liver graft.


RESULTS
Intragraft expression of FasL mRNA was constitutively expressed after adenovirus-mediated transduction, although expression of FasL increased mildly in control grafts. Bcl-2 mRNA was highly expressed at 2 days after reperfusion. In contrast, lower expression of bcl-2 was observed in the control group. The average survival of the gene transferred allografts increased from (9.8+1.3) days to (18.5+8.7) days compared with the control group.


CONCLUSIONS
Our results indicate that rat liver allografts can be protected against host immune responses by adenovirus-mediated FasL and bcl-2 transfection, and that bcl-2 expression prevents the graft from Fas-mediated apoptosis.
Wang
De-Sheng
DS
Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. wangdesh@163.com
Li
Yu
Y
Dou
Ke-Feng
KF
Li
Kai-Zong
KZ
Song
Zhen-Shun
ZS
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053222:Fas Ligand Protein / Q000235:genetics*; D019254:Genes, bcl-2; D006084:Graft Rejection / Q000473:pathology; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D023001:Transplantation Tolerance; D014184:Transplantation, Homologous
D053222:Fas Ligand Protein