Authors
Marcel Leist, Florian Gantner, Ines Bohlinger, Gisa Tiegs, Paul-Georg Germann, Albrecht Wendel
Publication date
1995/5
Journal
The American journal of pathology
Volume
146
Issue
5
Pages
1220
Publisher
American Society for Investigative Pathology
Description
We investigated the role of hepatocyte apoptosis in four different murine models of acute inflammatory liver failure. Liver damage induced in D-galactosamine-sensitized mice by endotoxin infection was initiated by processes typical of apoptosis, ie, chromatin condensation, DNA fragmentation, and formation of intracellular apoptotic bodies. DNA was cleaved into oligonucleosomal fragments in the liver before a significant rise of alanine aminotransferase in plasma occurred. Passive immunization against tumor necrosis factor (TNF) completely inhibited the injury caused by endotoxin. Direct injection of recombinant TNF-alpha also caused DNA fragmentation followed by alanine aminotransferase release into the plasma. Pretreatment of mice with interleukin-1 beta, which is known to suppress TNF-induced lethality, completely prevented apoptosis and liver failure in this model. These results demonstrate the causal …
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M Leist, F Gantner, I Bohlinger, G Tiegs, PG Germann… - The American journal of pathology, 1995