Endotoxin-inducible cytotoxicity in liver cell cultures-I

T. Hartung, A. Wendel

Research output: Contribution to journalArticlepeer-review

Abstract

It is known that rodents challenged with a combination of galactosamine and endotoxin develop a fulminant hepatitis within several hours. Until now, no in-vitro correlate for this organ-specific lesion has been described. Here, in-vitro conditions have been developed which allow examination of lipopolysaccharide (endotoxin)-inducible cell injury to hepatocytes. Under these in-vitro conditions (RPMI 1640 supplemented with 10% calf serum, 40% oxygen tension) which require the presence of functionally intact Kupffer cells, a concentration-dependent lactate dehydrogenase release is inducible by different lipopolysaccharides in hepatocyte cultures from Fischer rats. It can be abrogated by polymyxin B. These co-cultures secreted tumor necrosis factor-α into the medium upon a lipo-polysaccharide stimulus. The presence of a tumor necrosis factor-α antiserum reduced the major part of the endotoxin-inducible cytotoxicity. Similarities in vitro and in vivo of the cytotoxic potency of various endotoxin species and the different responsiveness of hepatocytes from two different rat strains support that this co-culture system might be useful for studying endotoxin-inducible lesions in vitro.

Original languageEnglish (US)
Pages (from-to)1129-1135
Number of pages7
JournalBiochemical Pharmacology
Volume42
Issue number5
DOIs
StatePublished - Aug 8 1991
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

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