Fas receptor is upregulated in livers from non-heart-beating donors.
Cell injury in livers from non-heart-beating donors (NHBDs) is not only caused by necrosis, but it is increasingly being recognized that apoptotic transformation contributes to postischemic cell death. It remains unclear which pathways lead to apoptosis. We suggested that apoptosis in NHBD livers might be mediated by the Fas receptor. Therefore the aim of our study was the detection and quantification of the Fas receptor, Fas mRNA and apoptosis in NHBD livers. Livers of male Wistar rats were harvested either from heart-beating donors (control, n = 15) or 30 min after cardiac arrest from NHBDs (n = 15). All livers were stored in University of Wisconsin solution for 24 h at 4 degrees C, and reperfused using a recirculating model with oxygenated Krebs-Henseleit buffer for 120 min at 37 degrees C. Conventional signs of cell damage, such as enzyme release and bile production, showed an elevated nonspecific cell injury in NHBD livers. The immunohistochemical staining of Fas antigen expression revealed a 7% rate of Fas receptor-expressing hepatocytes in the control group, but a considerable increase up to 38% in the NHBD group. No Fas antigen expression was detected on sinusoidal endothelial cells. Real-time RT-PCR detected an approximately eightfold elevated concentration of Fas mRNA transcripts in NHBD livers. We conclude that upregulation of the Fas receptor on hepatocytes in NHBDs will prime these cells to eventually undergo apoptosis upon reperfusion in vivo. Therefore, therapeutic modulation of the Fas pathway must be considered as a new strategy in order to additionally protect NHBD livers which are otherwise prone to parenchymal apoptosis.
Schnurr
C
C
Division of Surgical Research, Surgical Clinic, University of Bonn, Germany.
Glatzel
U
U
Tolba
R
R
Hirner
A
A
Minor
T
T
D000818:Animals; D017209:Apoptosis; D006323:Heart Arrest; D008099:Liver / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting; D015854:Up-Regulation; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D019014:fas Receptor