MAdCAM-1 expressed in chronic inflammatory liver disease supports mucosal lymphocyte adhesion to hepatic endothelium (MAdCAM-1 in chronic inflammatory liver disease)

Hepatology. 2001 May;33(5):1065-72. doi: 10.1053/jhep.2001.24231.


Mucosal addressin cell adhesion molecule (MAdCAM-1) plays a pivotal role in T-lymphocyte homing to the gut. Given the strong association between the autoimmune liver diseases primary sclerosing cholangitis and autoimmune hepatitis and inflammatory bowel disease, we investigated the role of MAdCAM-1 in recruiting mucosal lymphocytes to the liver. MAdCAM-1 was strongly expressed on inflamed portal vein/sinusoidal endothelium in autoimmune mediated liver disease. In modified Stamper-Woodruff assays, MAdCAM-1 on hepatic vessels supported adhesion of alpha4beta7+ lymphocytes (i.e., gut-derived T cells) from patients with inflammatory bowel disease and primary sclerosing cholangitis. This adhesion was inhibited by pretreatment with blocking antibodies to MAdCAM-1, alpha4beta7, or the integrin alpha4 chain indicating that MAdCAM-1 in inflamed liver is functionally active. Circulating lymphocytes from patients with primary sclerosing cholangitis showed rolling adhesion on MAdCAM-1 transfectants in a flow-based adhesion assay that could be blocked by anti-MAdCAM-1 or anti-alpha4beta7 mAbs. These findings indicate that, under certain circumstances, vessels in the human liver support adhesion of alpha4beta7+ mucosal lymphocytes via binding to aberrantly expressed MAdCAM-1 on liver endothelium. This provides a mechanism to explain the hepatic recruitment of mucosal lymphocytes in inflammatory liver disease complicating inflammatory bowel disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blood Cells / metabolism
  • Cell Adhesion / physiology
  • Cell Adhesion Molecules
  • Cholangitis, Sclerosing / pathology
  • Cholangitis, Sclerosing / physiopathology
  • Chronic Disease
  • Endothelium, Vascular / pathology
  • Endothelium, Vascular / physiopathology*
  • Hepatitis / physiopathology*
  • Humans
  • Immunoglobulins / physiology*
  • Inflammatory Bowel Diseases / pathology
  • Inflammatory Bowel Diseases / physiopathology
  • Integrins / metabolism
  • Intestinal Mucosa / pathology
  • Intestinal Mucosa / physiopathology*
  • Liver / pathology
  • Liver / physiopathology*
  • Lymphocytes / physiology*
  • Mucoproteins / physiology*


  • Cell Adhesion Molecules
  • Immunoglobulins
  • Integrins
  • MADCAM1 protein, human
  • Mucoproteins
  • integrin alpha4beta7