Cell
Volume 74, Issue 1, 16 July 1993, Pages 185-195
Journal home page for Cell

Article
α4β7 integrin mediates lymphocyte binding to the mucosal vascular addressin MAdCAM-1

https://doi.org/10.1016/0092-8674(93)90305-AGet rights and content

Abstract

The mucosal vascular addressin, MAdCAM-1, is an immunoglobulin superfamily adhesion molecule for lymphocytes that is expressed by mucosal venules and helps direct lymphocyte traffic into Peyer's patches (PP) and the intestinal lamina propria. We demonstrate that the lymphocyte integrin α4β7, also implicated in homing to PP, is a receptor for MAdCAM-1. Certain antibodies to α4 and β7 integrin chains but not to the β2 integrin LFA-1 inhibit lymphocyte binding to purified MAdCAM-1 and to MAdCAM-1 transfectants. Lymph node lymphocytes, α4β7+ TK1 lymphoma cells, and a β7-transfected variant of an α4+ B cell line, 38C13, bind constitutively to MAdCAM-1. Binding is enhanced by Mn++-induced integrin activation. The related integrin α4β1 supports efficient binding to VCAM-1 but not to MAdCAM-1, even after integrin activation, indicating that MAdCAM-1 is a preferential ligand for α4β7. α4β7 can also bind VCAM-1, but this requires greater integrin activation than binding to MAdCAM-1. The findings imply a selective role for the interaction of α4β7 and MAdCAM-1 lymphocyte in homing to mucosal sites.

References (61)

  • R.O. Hynes

    Integrins: versatility, modulation, and signaling in cell adhesion

    Cell

    (1992)
  • D. Kirchhofer et al.

    Cation-dependent changes in the binding specificity of the platelet receptor GPIIbIIIa

    J. Biol. Chem.

    (1990)
  • L.A. Lasky et al.

    An endothelial ligand for L-selectin is a novel mucin-like molecule

    Cell

    (1992)
  • R. Pulido et al.

    Functional evidence for three distinct and independently inhibitable adhesion activities mediated by the human integrin VLA-4

    Correlation with distinct α4 epitopes

    J. Biol. Chem.

    (1991)
  • Y. Shimizu et al.

    Lymphocyte interactions with endothelial cells

    Immunol. Today

    (1992)
  • D.E. Staunton et al.

    The arrangement of the immunoglobulin-like domains of ICAM-1 and the binding sites for LFA-1 and rhinovirus

    Cell

    (1990)
  • Q. Yuan et al.

    Molecular cloning of the mouse integrin β7 subunit

    J. Biol. Chem.

    (1992)
  • M.M. Zatz et al.

    The distribution of chromium 51-labelled lymphoid cells in the mouse

    Cell. Immunol.

    (1970)
  • A. Ager et al.

    Use of synthetic peptides to probe lymphocyte-high endothelial cell interactions: lymphocytes recognize a ligand on the endothelial surface which contains the CS1 adhesion motif

    Int. Immunol.

    (1990)
  • R.F. Bargatze et al.

    Rapid G protein-regulated activation event involved in lymphocyte binding to high endothelial venules

    J. Exp. Med.

    (1993)
  • E.L. Berg et al.

    The human peripheral lymph node vascular addressin is a ligand for LECAM-1, the peripheral lymph node homing receptor

    J. Cell Biol.

    (1991)
  • M.J. Briskin et al.

    MAdCAM-1 displays homology to immunglobulin and mucin-like adhesion receptors and to IgA

    Nature

    (1993)
  • E.C. Butcher

    The regulation of lymphocyte traffic

    Curr. Topics Microbiol. Immunol.

    (1986)
  • E.C. Butcher et al.

    Organ specificity of lymphocyte migration: mediation by highly selective lymphocyte interaction with organ-specific determinants of high endothelial venules

    Eur. J. Immunol.

    (1980)
  • M. Culty et al.

    The hyaluronate receptor is a member of the CD44 (H-CAM) family of cell surface glycoproteins

    J. Cell. Biol.

    (1990)
  • I. Dransfield et al.

    Divalent cation regulation of the function of the leukocyte integrin LFA-1

    J. Cell Biol.

    (1992)
  • M.J. Elices et al.

    Receptor functions for the integrin VLA-3: fibronectin, collagen, and laminin binding are differentially influenced by ARG-GLY-ASP peptide and by divalent cations

    J. Biol. Chem.

    (1991)
  • J. Fawcett et al.

    Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes

    Nature

    (1992)
  • W.M. Gallatin et al.

    A cell surface molecule involved in organ-specific homing of lymphocytes

    Nature

    (1983)
  • A. Garcia-Pardo et al.

    Human B lymphocytes define an alternative mechanism of adhesion to fibronectin

    The interaction of the α4β1 integrin with the LHGPEILDVPST sequence of the type III connecting segment is sufficient to promote cell attachment

    J. Immunol.

    (1990)
  • Cited by (0)

    View full text