ICAM-1 is involved in the mechanism of alcohol-induced liver injury: studies with knockout mice. Academic Article uri icon

abstract

  • 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.

published proceedings

  • Am J Physiol Gastrointest Liver Physiol

author list (cited authors)

  • Kono, H., Uesugi, T., Froh, M., Rusyn, I., Bradford, B. U., & Thurman, R. G.

citation count

  • 63

complete list of authors

  • Kono, H||Uesugi, T||Froh, M||Rusyn, I||Bradford, BU||Thurman, RG

publication date

  • June 2001