title: Utility of adenovirus-mediated Fas ligand and bcl-2 gene transfer to modulate rat liver allograft survival.
abstract: 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.
authors.affiliation: Department of Hepatobiliary Surgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. wangdesh@163.com
authors.forename: De-Sheng
authors.initials: DS
authors.lastname: Wang
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.forename: Ke-Feng
authors.initials: KF
authors.lastname: Dou
authors.forename: Kai-Zong
authors.initials: KZ
authors.lastname: Li
authors.forename: Zhen-Shun
authors.initials: ZS
authors.lastname: Song
mesh_terms: 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
chemical_list: D053222:Fas Ligand Protein