THE FAS FAS-LIGAND SYSTEM FUNCTIONS IN HEPATOCYTES IN THE EARLY-STAGEOF FULMINANT HEPATIC-FAILURE IN RATS/

Apoptosis is involved in various liver diseases, but in the case of fu lminant hepatic failure (FHF) much remains to be determined. We invest igated apoptosis in the remnant liver lobes of FHF rats regarding the Fas/Fas ligand and the TGF-beta system. Rats (n = 30) with FHF were eu thanized at postoperative 3, 6, 12, 24 and 36 h. Changes in the Fas/Fa s-ligand and TGF-beta were studied by reverse transcriptase-polymerase chain reaction (RT-PCR) and immunohistochemical staining. Apoptosis w as explored using terminal deoxynucleotidyl transferase mediated dUDP- nick end labeling method (TUNEL). Within 6 h, a relatively large numbe r of hepatocytes, mainly in zone 3, were apoptotic. During the same pe riod, the expression of Fas and Fas-ligand mRNA and protein, but not t hat of TGF-beta, were observed and decreased with time. Both Fas and F as-ligand proteins were present in the hepatocytes in zone 3. These re sults suggest that the Fas/Fas-ligand system, rather than TGF-beta, ha s a role in apoptosis during the early stages of FHF, possibly through an autocrine loop. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.