title: Prolonged survival of rat liver allografts transfected with Fas ligand-expressing plasmid.
abstract: BACKGROUND
  Transplantation of Fas ligand (FasL) gene-transfected tissues can have opposite effects. For example, cotransplantation of pancreas islets with myoblasts transfected with FasL-expressing plasmid vector (pFasL) prevented graft rejection, whereas the expression of FasL directly within islets using adenovirus vector led to graft destruction. It was also reported that FasL expression on pancreas islets led to neutrophilic infiltration and rapid destruction of the islets. From these results, overexpression of FasL in transfected tissues may lead directly to self destruction through an autocrine Fas-FasL pathway or graft destruction through neutrophil recruitment. To date there have been no reports of successful transplantation of FasL gene-transfected solid organs.
  
  
  METHODS
  Rat pFasL was transfected at a dose of 90, 180, 270, or 360 microg into rat liver with an inactivated hemagglutinating virus of Japan conjugated to liposome vesicles (HVJ-liposome), and the gene-transfected livers were transplanted to allogeneic rats.
  
  
  RESULTS
  In 18 rats transfected with 180 microg of pFasL, 14 (78%) did not develop fulminant hepatitis. FasL-mRNA was detected in these livers at 3, 5, 7, and 14 days after transfection. The expression of FasL protein was also observed in the transfected liver, and the transfection rate by this method was 11.1+/-1.9%. The livers were then transplanted to allogeneic recipients, resulting in significant (P<0.01) prolonged recipient survival times. Histological observation showed that the pFasL-transfected liver allografts caused apoptotic cell death in infiltrating activated T cells. In contrast, transfection of pFasL higher than 180 microg resulted in lethal hepatitis in all rats, and its low dose (90 microg) did not induce the hepatitis or prolong recipient survival.
  
  
  CONCLUSIONS
  Our results indicate that rat liver allografts can be protected to host immune responses by an adequate level (approximately 10%) of FasL expression in the livers using HVJ-liposome incorporating pFasL.
authors.affiliation: Department of Experimental Surgery & Bioengineering, National Children's Medical Research Center, Tokyo, Japan.
authors.forename: X K
authors.initials: XK
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Okuyama
authors.forename: A
authors.initials: A
authors.lastname: Tamura
authors.forename: S
authors.initials: S
authors.lastname: Enosawa
authors.forename: Y
authors.initials: Y
authors.lastname: Kaneda
authors.forename: S
authors.initials: S
authors.lastname: Takahara
authors.forename: N
authors.initials: N
authors.lastname: Funashima
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Amemiya
authors.forename: S
authors.initials: S
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D004396:Coloring Agents; D053222:Fas Ligand Protein; D015870:Gene Expression; D006085:Graft Survival / Q000235:genetics; D006505:Hepatitis / Q000473:pathology; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000473:pathology; D016031:Liver Transplantation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000235:genetics*; D010957:Plasmids / Q000235:genetics*; D051381:Rats; D013997:Time Factors; D014162:Transfection; D014184:Transplantation, Homologous / Q000502:physiology; D001616:beta-Galactosidase / Q000032:analysis
chemical_list: D004396:Coloring Agents; D053222:Fas Ligand Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D001616:beta-Galactosidase