Blocking MAdCAM-1 in vivo reduces leukocyte extravasation and reverses chronic inflammation in experimental colitis

Int J Colorectal Dis. 2006 Jan;21(1):71-8. doi: 10.1007/s00384-004-0709-y. Epub 2005 Apr 23.


Background: Leukocyte recruitment to sites of intestinal inflammation is a crucial multi-step process, leading ultimately to the accumulation of cells in the inflamed tissue. These interactions in the gut are critically dependent on the mucosal addressin cell adhesion molecule-1 (MAdCAM-1), which is expressed on endothelial cells within the mesenteric lymph nodes and the lamina propria of the intestine. Here, we investigate the pathophysiologic role of MAdCAM-1 in the intestinal microcirculation in vivo.

Methods: Using a standard mouse model, chronic colitis was established after four cycles of dextran sodium sulfate (DSS) application. MAdCAM-1 expression was investigated by immunohistochemistry and Western blotting, as well as real-time polymerase chain reaction (PCR). Intravital microscopy was used to study the role of MAdCAM-1 on leukocyte-endothelium interactions and leukocyte extravasation.

Results: Significant changes in MAdCAM-1 were observed in mice with chronic DSS-induced colitis. Upregulation of MAdCAM-1 expression in chronic colitis was demonstrated on a protein and messenger ribonucleic acid (mRNA) level. Anti-MAdCAM-1 treatment lead to a marked reduction (>60%) of leukocyte sticking and extravasation in vivo, compared to the controls. This was parallelled by a significant reduction (45%) of intestinal inflammation, as measured by the histologic grading score.

Conclusion: These in vivo results demonstrate a distinct role of MAdCAM-1 in inflammatory intestinal diseases, and suggest that therapeutic strategies targeting this adhesion molecule could be useful in the treatment of chronic colitis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / pharmacology*
  • Blotting, Western
  • Cell Adhesion Molecules / drug effects
  • Cell Adhesion Molecules / metabolism*
  • Cell Movement / physiology*
  • Colitis / metabolism
  • Colitis / pathology*
  • Dextran Sulfate
  • Disease Models, Animal
  • Endothelium, Vascular / immunology
  • Female
  • Immunohistochemistry
  • Inflammation Mediators / analysis
  • Intercellular Adhesion Molecule-1 / analysis
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Leukocytes
  • Mice
  • Mice, Inbred BALB C
  • Mucoproteins
  • Polymerase Chain Reaction / methods
  • Probability
  • Sensitivity and Specificity
  • Statistics, Nonparametric


  • Antibodies, Antinuclear
  • Cell Adhesion Molecules
  • Inflammation Mediators
  • Madcam1 protein, mouse
  • Mucoproteins
  • Intercellular Adhesion Molecule-1
  • Dextran Sulfate