Acute Liver Failure

New apoptosis data have been reported by researchers at University of Rostock

Acute Liver Failure Library Library Home This article was published in Gastroenterology Week, which you can subscribe to online.

"First published March 5, 2009; doi:10.1152/ajpgi.90689.2008.-Cytotoxic T lymphocytes and their granule components, such as perforin and granzyme, play an important role in the defense of hepatic infections caused by different pathogens. Moreover, it has been shown in vitro that hepatocytes can initiate cell death via a perforin-dependent mechanism. Although it is well known that hepatocellular apoptosis in D-galactosamine/lipopoly-saccharide (D-Gal/LPS)-associated liver failure is mediated by TNF alpha-dependent Fas/FasL cytotoxicity, there is no information on the role of perforin-mediated mechanisms in vivo. Therefore, we studied whether the cytolytic perforin/granzyme pathway contributes to the D-Gal/LPS-associated hepatotoxicity. Perforin knockout (Pko) mice showed significantly higher hepatic TNF-alpha and IL-6 mRNA expression as well as plasma TNF-alpha and IL-6 concentrations within the first hour upon D-Gal/LPS challenge compared with perforin wild-type (Pwt) mice. At 6 h upon D-Gal/LPS challenge, Pko mice further presented with higher transaminase release and onconecrotic tissue damage, whereas hepatocellular apoptosis and caspase-3 cleavage remained unaffected by the perforin deficiency. Pretreatment with a recombinant human TNF-alpha receptor fusion protein attenuated necrotic and apoptotic tissue damage and reduced plasma transaminase activities as well as cytokine release, thereby preventing acute liver failure in Pko mice as effectively as in Pwt mice," wrote A. Kuhla and colleagues, University of Rostock.

The researchers concluded: "These data do not only confirm the significance of TNF-alpha as distal mediator of hepatic injury in this model but simultaneously reveal a contribution of a perforin-dependent immunoregulation, limiting the D-Gal/LPS-induced overwhelming cytokine release and onconecrotic tissue injury.."

Kuhla and colleagues published their study in American Journal of Physiology - Gastrointestinal and Liver Physiology (Role of the perforin/granzyme cell death pathway in D-Gal/LPS-induced inflammatory liver injury. American Journal of Physiology - Gastrointestinal and Liver Physiology, 2009;296(5):G1069-G1076).

For more information, contact B. Vollmar, University of Rostock, Institute Experimental Surgery, Schillingallee 69A, D-18055 Rostock, Germany.

Publisher contact information for the American Journal of Physiology - Gastrointestinal and Liver Physiology is: American Physiological Society, 9650 Rockville Pike, Bethesda, MD 20814, USA.

Keywords: Germany, Rostock, Apoptosis, Caspase, Enzyme Research, Gastroenterology, Hepatology, Liver Failure, Necrosis, Physiology, University of Rostock.

This article was prepared by Gastroenterology Week editors from staff and other reports. Copyright 2009, Gastroenterology Week via NewsRx.com.