ICAM-1 is involved in the mechanism of alcohol-induced liver injury: studies with knockout mice

To test the hypothesis that leukocyte infiltration mediated by intercellular adhesion molecule (ICAM)-1 is involved in early alcohol-induced liver injury, male wild-type or ICAM-1 knockout mice were fed a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin for 4 wk. There were no...

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Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2001-06, Vol.280 (6), p.G1289-G1295
Main Authors: Kono, H, Uesugi, T, Froh, M, Rusyn, I, Bradford, B U, Thurman, R G
Format: Article
Language:English
Subjects:
Alanine Transaminase - blood
Animals
Ethanol - urine
Intercellular Adhesion Molecule-1 - genetics
Intercellular Adhesion Molecule-1 - physiology
Liver - enzymology
Liver - pathology
Liver Diseases, Alcoholic - pathology
Liver Diseases, Alcoholic - physiopathology
Male
Mice
Mice, Inbred C57BL
Mice, Knockout - genetics
Neutrophils - pathology
Organ Size
Peroxidase - metabolism
RNA, Messenger - metabolism
Tumor Necrosis Factor-alpha - genetics
Weight Gain
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Summary:To test the hypothesis that leukocyte infiltration mediated by intercellular adhesion molecule (ICAM)-1 is involved in early alcohol-induced liver injury, male wild-type or ICAM-1 knockout mice were fed a high-fat liquid diet with either ethanol or isocaloric maltose-dextrin for 4 wk. There were no differences in mean urine alcohol concentrations between the groups fed ethanol. Alcohol administration significantly increased liver size and serum alanine aminotransferase levels in wild-type mice over high-fat controls, effects that were blunted significantly in ICAM-1 knockout mice. Dietary ethanol caused severe steatosis, mild inflammation, and focal necrosis in livers from wild-type mice. Furthermore, livers from wild-type mice fed ethanol showed significant increases in the number of infiltrating leukocytes, which were predominantly lymphocytes. These pathological changes were blunted significantly in ICAM-1 knockout mice. Tumor necrosis factor (TNF)-alpha mRNA expression was increased in wild-type mice fed ethanol but not in ICAM-1 knockout mice. These data demonstrate that ICAM-1 and infiltrating leukocytes play important roles in early alcohol-induced liver injury, most likely by mechanisms involving TNF-alpha.
ISSN:0193-1857
1522-1547
DOI:10.1152/ajpgi.2001.280.6.G1289