Human mucosal addressin cell adhesion molecule-1 (MAdCAM-1) demonstrates structural and functional similarities to the alpha 4 beta 7-integrin binding domains of murine MAdCAM-1, but extreme divergence of mucin-like sequences

J Immunol. 1996 Apr 15;156(8):2851-7.

Abstract

The mucosal vascular addressin, mucosal addressin cell adhesion molecule-1 (MAdCAM-1), is an Ig family adhesion receptor preferentially expressed by venular endothelial cells at sites of lymphocyte extravasation in murine mucosal lymphoid tissues and lamina propria. MAdCAM-1 specifically binds both human and mouse lymphocytes that express the homing receptor for Peyer's patches, the integrin alpha 4 beta 7. Functional expression cloning was used to isolate a cDNA from a macaque mesenteric lymph node library that encodes the homologue to murine MAdCAM-1. The macaque cDNA was subsequently used to clone the human homologue as well. Expression of human MAdCAM-1 RNA is restricted to mucosal tissues, gut-associated lymphoid tissues and spleen. Human MAdCAM-1 selectively binds both murine and human lymphocyte cell lines expressing alpha 4 beta 7. Human and macaque MAdCAM-1 have two Ig-like domains that are similar to the two amino-terminal integrin binding domains of murine MAdCAM-1. The conservation of sequences within the region homologous to the mucin/IgA domain of murine MAdCAM-1 is, however, much less apparent. These receptors exhibit considerable variation from murine MAdCAM-1 with respect to the length of the mucin-like sequence and the lack of a membrane proximal Ig (IgA-like) domain. The isolation of these different species of MAdCAM-1 demonstrates greater seleoffctive pressure for maintenance of amino acids involved in alpha 4 beta 7 binding than those sequences presumably involved in the presentation of carbohydrates for selectin binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Adhesion Molecules
  • Cloning, Molecular
  • Humans
  • Immunoglobulins / chemistry*
  • Immunoglobulins / genetics
  • Immunoglobulins / physiology*
  • Integrins / chemistry*
  • Integrins / genetics
  • Integrins / physiology*
  • Intestinal Mucosa / chemistry
  • Intestinal Mucosa / immunology*
  • Macaca
  • Mice
  • Molecular Sequence Data
  • Mucins / chemistry*
  • Mucins / genetics
  • Mucins / physiology*
  • Mucoproteins / chemistry*
  • Mucoproteins / genetics
  • Mucoproteins / physiology*
  • RNA, Messenger / biosynthesis
  • Sequence Homology, Amino Acid*

Substances

  • Cell Adhesion Molecules
  • Immunoglobulins
  • Integrins
  • MADCAM1 protein, human
  • Madcam1 protein, mouse
  • Mucins
  • Mucoproteins
  • RNA, Messenger
  • integrin alpha4beta7

Associated data

  • GENBANK/U43628