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Updated: Aug 9, 2026
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
Role of intercellular adhesion molecule-1 and lymphocyte function-associated antigen-1 during nonsuppurative
C D Howell1, J Li, W Chen
1The University of Maryland at Baltimore, School of Medicine, Baltimore, MD, USA. chowell@umaryland.edu
Insights
Intercellular adhesion molecule-1 (ICAM-1) and its receptor lymphocyte function-associated antigen-1 (LFA-1) play key roles in nonsuppurative destructive cholangitis (NSDC) pathogenesis. Blocking ICAM-1 and LFA-1 pathways can reduce bile duct damage and inflammation in a mouse model.
Area of Science:
- Immunology
- Hepatology
- Pathology
Background:
- Abnormal intercellular adhesion molecule-1 (ICAM-1) expression occurs in primary biliary cirrhosis (PBC).
- The role of ICAM-1 and its receptor, lymphocyte function-associated antigen-1 (LFA-1), in nonsuppurative destructive cholangitis (NSDC) remains undefined.
Purpose of the Study:
- To investigate the relationship between ICAM-1 expression and NSDC lesion development in a mouse graft-versus-host disease (GVHD) model.
- To evaluate the therapeutic effects of anti-ICAM-1 and anti-LFA-1 treatments on NSDC, lymphokine production, and lymphocyte homing.
Main Methods:
- Utilized a mouse GVHD model to study NSDC.
- Administered anti-ICAM-1 and anti-LFA-1 antibodies.
- Assessed histological damage, portal inflammation, intrahepatic lymphokine levels (IL-2, IL-12, IL-4, IL-10, interferon-gamma), and lymphocyte homing.
Main Results:
- ICAM-1 expression correlated positively with bile duct damage in GVHD mice.
- Anti-ICAM-1 treatment significantly reduced portal inflammation and NSDC lesions.
- Combined anti-ICAM-1 and anti-LFA-1 treatment further decreased inflammation and bile duct damage.
- Anti-ICAM-1 treatment reduced T cell percentages and IL-2/IL-12 production in the liver.
Conclusions:
- ICAM-1 and LFA-1 are crucial in the pathogenesis of NSDC.
- Targeting ICAM-1 and LFA-1 pathways shows therapeutic potential for reducing liver inflammation and bile duct injury.
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.
