The role of lipopolysaccharide and tumor necrosis factor-alpha in
the induction of hepatocyte necrosis.
Wang, Jiang-Huai, H. Paul Redmond, R. William G. Watson, and David
Bouchier-Hayes.
Department of Surgery, The Royal College of Surgeons in Ireland,
Beaumont Hospital, Dublin 9, Ireland
APStracts 2:0062G, 1995.
The occurrence of acute hepatic failure during systemic inflammatory
response syndrome (SIRS) is related to the extent of hepatocyte (HC)
damage and cell death resulting from necrosis or apoptosis. We
hypothesized that proinflammatory mediators such as
lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF) can,
either directly or indirectly through neutrophil (PMN) and Kupffer
cell (KC) activation, induce HC damage and cell death, and that the
mechanism is cellular necrosis rather than apoptosis. The results in
this study demonstrated that LPS alone, TNF alone, and in combination
are directly cytotoxic to cultured rat HCs as indicated by the
hepatocellular enzyme release and HC necrosis. However LPS and TNF,
in the presence of sodium arsenite (a heat shock inducer), were
unable to induce HC apoptosis. Both KCs and PMNs activated by either
LPS or TNF induced significant hepatocellular enzyme release and HC
necrosis, which was dependent on the ratio of KCs and PMNs to HCs. It
is concluded that LPS and TNF may play a central role in the
development of acute hepatic failure following severe trauma and
sepsis by directly or indirectly inducing HC necrosis rather than
apoptosis.
Received 14 June 1994; accepted in final form 3 March 1995.
APS Manuscript Number G229-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.