Human mucosal addressin cell adhesion molecule-1 is preferentially expressed in intestinal tract and associated lymphoid tissue

Am J Pathol. 1997 Jul;151(1):97-110.

Abstract

Lymphocyte homing to normal tissues and recruitment to inflammatory tissue sites are controlled, in part, by the selective expression of chemokines, pro-inflammatory cytokines and mediators, and various adhesion proteins and molecules. In the mouse, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) is selectively expressed on endothelium of high endothelial venules in gut and gut-associated lymphoid tissue. By interaction with its integrin ligand, alpha 4 beta 7, lymphocytes presumed to be involved in mucosal immunity are selectively recruited to these intestinal sites. After generating monoclonal antibodies against a murine cell line expressing recombinant human MAdCAM-1, we qualitatively and semiquantitatively assessed MAdCAM-1 expression in human tissue sections from various normal and inflammatory disorders. We found that human MAdCAM-1, as in the mouse, is expressed in a tissue-selective manner. In normal tissues, MAdCAM-1 is constitutively expressed to endothelium of venules of intestinal lamina propria. Interestingly, using computer-assisted morphometric analysis, the proportion of venular endothelium within lamina propria that expresses MAdCAM-1 is increased, compared with normal tissues, at inflammatory foci associated with ulcerative colitis and Crohn's disease. Moreover, for the most part, MAdCAM-1 is not detected in the majority of normal or inflamed extra-intestinal tissues, including those with mucosal surfaces. These results are consistent with a role, as originally defined in the mouse, for human MAdCAM-1 in the localization of alpha 4 beta 7+ lymphocytes in the gastrointestinal tract and associated lymphoid tissue. As such, the pathway defined by MAdCAM-1/alpha 4 beta 7 may be a relevant tissue-specific therapeutic target for the modulation of inflammatory bowel disease activity.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Monoclonal / chemistry
  • CHO Cells
  • Cell Adhesion Molecules
  • Colon / metabolism
  • Cricetinae
  • Cross Reactions
  • Humans
  • Immunoglobulins / biosynthesis*
  • Immunoglobulins / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / metabolism*
  • Intestines / pathology
  • Lymphoid Tissue / metabolism*
  • Lymphoid Tissue / pathology
  • Lymphoma, B-Cell
  • Macaca mulatta
  • Mice
  • Mucoproteins / biosynthesis*
  • Mucoproteins / immunology
  • Receptors, Lymphocyte Homing / biosynthesis*
  • Receptors, Lymphocyte Homing / immunology
  • Tumor Cells, Cultured

Substances

  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Immunoglobulins
  • MADCAM1 protein, human
  • Madcam1 protein, mouse
  • Mucoproteins
  • Receptors, Lymphocyte Homing