Involvement of tumor necrosis factor-α in development of hepatic injury in galactosamine-sensitized mice
| Autor: | Takashi Yamanaka, Isao Yamatsu, Kazuo Tsukidate, Kaname Miyamoto, Kazuo Hirota, Junichi Nagakawa, Ieharu Hishinuma, Kouichi Katayama |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
Lipopolysaccharides
medicine.medical_specialty Pathology Necrosis Lipopolysaccharide Ratón Galactosamine Mice chemistry.chemical_compound Internal medicine Massive Hepatic Necrosis medicine Animals Cytotoxic T cell Aspartate Aminotransferases Cytotoxicity Mice Inbred C3H Hepatology Tumor Necrosis Factor-alpha business.industry Immune Sera Immunization Passive Alanine Transaminase Endocrinology Liver chemistry Tumor necrosis factor alpha medicine.symptom business |
| Zdroj: | Hepatology. 12:1187-1191 |
| ISSN: | 1527-3350 0270-9139 |
| DOI: | 10.1002/hep.1840120518 |
| Popis: | Intravenous injection of lipopolysaccharide and D-galactosamine, at doses of 0.2 μg/kg and 800 mg/kg, respectively, elicited massive hepatic necrosis within 24 hr in C3H/HeN mice. The plasma L-alanine aminotransferase (ALT, E.C. 2.6.1.2) or L-aspartate aminotransferase (AST, E.C. 2.6.1.1) activities at this point reached more than 2,000 IU/L. However, overt hepatic injury as evaluated by the plasma aminotransferase activities did not develop in mice in which only lipopolysaccharide or only D-galactosamine was injected. No tumor necrosis factor—like activities could be detected in the plasma of galactosamine- and lipopolysaccharide-injected mice as determined by the assay of cytotoxicity to highly tumor necrosis factor—sensitive L-P3 cells through the experimental period of 24 hr. However, passive immunization against mouse tumor necrosis factor—α with polyvalent rabbit anti-mouse tumor necrosis factor—α antiserum, which was able to neutralize the cytotoxic effects of recombinant mouse tumor necrosis factor—α on L-P3 cells, could protect the mice from the development of hepatic injury in a dose-dependent manner. Simultaneous injection of recombinant human tumor necrosis factor—α, instead of lipopolysaccharide, with 800 mg/kg of D-galactosamine in lipopolysaccharide-resistant C3H/HeJ mice sensitized the animals more than one thousand-fold to the development of hepatic injury. The livers appeared to be morphologically similar to those of galactosamine- and lipopolysaccharide-injected C3H/HeN mice. These results suggest that endogenous tumor necrosis factor—α participates in the pathogenesis of lipopolysaccharide-elicited hepatic injury, and that tumor necrosis factor plays a crucial role in the development of liver necrosis in galactosamine-sensitized mice. (HEPATOLOGY 1990;12:1187–1191). |
| Databáze: | OpenAIRE |
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