Role of intercellular adhesion molecule-1 and lymphocyte function- associated antigen-1 during nonsuppurative destructive cholangitis in a mouse graft-versus-host disease model

Charles D. Howell, Jian Li, Weiran Chen

Research output: Contribution to journalArticle

Abstract

Intercellular adhesion molecule-1 (ICAM-1) is expressed abnormally on the bile duct epithelium during the course of primary biliary cirrhosis (PBC), but the importance of ICAM-1 and its lymphocyte function-associated antigen-1 (LFA-1) receptor during the course of nonsuppurative destructive cholangitis (NSDC) has not been defined. To address this question, we defined the relationship between ICAM-1 on the intrahepatic bile duct epithelium and the evolution of NSDC lesions in a mouse graft-versus-host disease (GVHD) model. We also determined the effects of anti-ICAM-1 and anti-LFA-1 treatments on NSDC, intrahepatic lymphokine production, and the homing of lymphocytes to the livers of GVHD mice. ICAM-1 was initially detected on the bile duct epithelium and portal vein endothelium on day 7 of GVHD. There was a significant positive correlation between the intensity of ICAM-1 staining and histological bile duct damage (r = .58, P < .05) between day 3 and 28. Treatment with anti-ICAM-1 (but not anti-LFA-1) decreased both the mean grades of portal inflammation (P = .003) and NSDC (P = .002) lesions compared with control immunoglobulin G (IgG) treatments. Combined treatment with anti- ICAM-1 and anti-LFA-1 caused a further decrease in the amount of portal inflammation and bile duct damage compared with anti-ICAM-1, alone (P = .02). Anti-ICAM-1 treatment also decreased both the percentage of T cells and the production of interleukin-2 (IL-2) and IL-12 in the liver (P < .01), but had no effect on IL-4, IL-10, and interferon gamma. Neither anti-ICAM-1 nor anti- LFA-1 prevented lymphocytes from homing to the liver. These results indicate that both ICAM-1 and LFA-1 are important to the pathogenesis of NSDC.

Original languageEnglish (US)
Pages (from-to)766-776
Number of pages11
JournalHepatology
Volume29
Issue number3
DOIs
StatePublished - Jan 1 1999

ASJC Scopus subject areas

  • Hepatology

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