Adenovirus-mediated expression of Fas ligand induces hepatic apoptosis after Systemic administration and apoptosis of ex vivo-infected pancreatic islet allografts and isografts.
Fas ligand (FasL) mediates apoptosis of Fas-bearing cells and is expressed on a limited number of tissues, predominantly activated T lymphocytes. We describe the construction and biological activity of a replication-deficient type-5 adenovirus encoding murine FasL under the control of the cytomegalovirus (CMV) promoter (adCMV-FasL). In vitro, Jurkat cells undergo apoptosis when co-incubated with adCMV-FasL-infected COS cells. Systemic administration of adCMV-FasL to Wistar rats or DBA/2J mice results in widespread hepatic apoptosis and death in a dose-dependent manner within 72 hr, an effect not seen in lpr mice, or animals administered equivalent doses of adCMV-beta gal. Murine pancreatic islets also undergo apoptosis when infected ex vivo with adCMV-FasL, resulting in uniform primary nonfunction when transplanted into syngeneic or allogeneic diabetic recipients. These results indicate that adCMV-FasL is a potentially useful tool to study Fas/FasL biology.
Muruve
D A
DA
Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA, USA.
Nicolson
A G
AG
Manfro
R C
RC
Strom
T B
TB
Sukhatme
V P
VP
Libermann
T A
TA
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D005822:Genetic Vectors; D007273:Injections, Intramuscular; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D017208:Rats, Wistar; D014161:Transduction, Genetic; D014184:Transplantation, Homologous; D014185:Transplantation, Isogeneic; D014779:Virus Replication / Q000235:genetics; D019014:fas Receptor / Q000096:biosynthesis*
D019014:fas Receptor