Inhibition of apoptosis reduces immunogeneic potential of adenoviral-treated syngeneic liver grafts.
Effects of adenoviral therapy and reduced apoptosis on immune response were investigated in a rat liver transplantation model after prolonged ischemia-reperfusion. Liver donors were treated i.v. either with an adenoviral construct, expressing bcl-2, green-fluorescent-protein, or doxycyclin. Intrahepatic apoptosis was assessed by terminal transferase dUTP nick end labeling assay. The intrahepatic presence of CD4, CD8a, CD163, immunoglobulin (Ig)beta, tumor necrosis factor (TNF)-alpha and myeloperoxidase (MPO) was quantified by realtime polymerase chain reaction at 24 hours and seven days after transplantation. Bcl-2 expression abrogated the TNF-alpha elevation and reduced apoptosis of hepatocytes and sinusoidal endothelial cells as compared to advCMV green fluorescent protein. No effects on CD4, CD8a, CD163 and MPO expression were noticed in bcl-2 pretreated livers, whereas Igbeta was slightly enhanced compared to controls. Adenoviral infected liver grafts trigger an immune response but reduced apoptosis resulted in down-regulation of TNF-alpha. Thus, bcl-2 transfer might simultaneously reduce graft ischemia reperfusion injury and immunogenicity.
Puellmann
Kerstin
K
Department of Internal Medicine II, University of Regensburg, Regensburg, Germany.
Beham
Alexander
A
Kienle
Klaus
K
Vogel
Mandy
M
Schlitt
Hans Juergen
HJ
Jauch
Karl Walter
KW
Rentsch
Markus
M
D000818:Animals; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D003587:Cytomegalovirus / Q000235:genetics*; D005819:Genetic Markers; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D020287:In Situ Nick-End Labeling; D016031:Liver Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D011994:Recombinant Proteins / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014185:Transplantation, Isogeneic
D005819:Genetic Markers; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D049452:Green Fluorescent Proteins