Cytokine-induced upregulation of hepatic intercellular adhesion molecule-1 messenger RNA expression and its role in the pathophysiology of murine endotoxin shock and acute liver failure
✍ Scribed by Naeem A. Essani; Michael A. Fisher; Anwar Farhood; Anthony M. Manning; C. Wayne Smith; Hartmut Jaeschke
- Publisher
- John Wiley and Sons
- Year
- 1995
- Tongue
- English
- Weight
- 972 KB
- Volume
- 21
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Neutrophil-induced liver injury during endotoxemia is dependent on the adhesion molecule Mac-1 (CD11W CD18) on neutrophils. The potential involvement of its counterreceptor, intercellular adhesion molecule-1 (ICAM-l), in the pathogenesis was investigated after administration of 100 pgikg Salmonella abortus equi endotoxin (ET) in galactosamine-sensitized mice (Gal). In ETsensitive mice (C3Heb/FeJ), which generated large amounts of tumor necrosis factor-alpha (TNF-a), massive neutrophil infiltration and severe liver injury were observed. In an ET-resistant strain (C3WHeJ), which did not generate TNF-a, GaUET failed to cause neutrophil accumulation or injury. ICAM-1 messenger RNA (mRNA), negligible in control livers, was selectively induced by GaUET in ET-sensitive mice. Intravenous injection of murine TNF-a, interleukin-1 alpha (IL-la) or ILlp (13 to 23 p e g ) strongly induced the ICAM-1 message in both strains, showing a comparable capacity for ICAM-1 mRNA synthesis. All cytokines caused similar neutrophil accumulation in the liver; however, only Gal! "?-a also caused upregulation of Mac-1 on circulating neutrophils and liver injury. The anti-murine ICAM-1 monoclonal antibody YN.l (3 m e g ) attenuated liver injury in ET-sensitive mice by 67% to 90% compared with isotype-matched control antibody-treated animals but did not reduce neutrophil accumulation in hepatic sinusoids. Our data suggest that the cytokines TNF-cu and IL-1 are the main mediators responsible for upregulation of ICAM-1 mRNA in the liver during endotoxemia. The upregulation of both adhesion molecules, ICAM-1