VCAM-1 on activated endothelium interacts with the leukocyte integrin VLA-4 at a site distinct from the VLA-4/fibronectin binding site

Cell. 1990 Feb 23;60(4):577-84. doi: 10.1016/0092-8674(90)90661-w.


Cytokine-activated human endothelial cells express vascular cell adhesion molecule-1 (VCAM-1), which binds lymphocytes. We now identify the integrin VLA-4 as a receptor for VCAM-1 because VLA-4 surface expression on K-562 cells (following transfection of the VLA alpha 4 subunit cDNA) resulted in specific cell adhesion to VCAM-1, and anti-VLA-4 antibodies completely inhibited VCAM-1-dependent cell-cell attachment. In addition, VLA-4 expression allowed K-562 cells to attach to the heparin II binding region (FN-40) of fibronectin. However, VLA-4/VCAM-1 and VLA-4/FN-40 interactions are readily distinguishable: only the former was inhibited by the anti-VLA-4 monoclonal antibody HP1/3, and only the latter was inhibited by soluble FN-40. The VCAM-1/VLA-4 ligand-receptor pair may play a major role in the recruitment of mononuclear leukocytes to inflammatory sites in vivo.

Publication types

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

MeSH terms

  • Animals
  • Antibodies, Monoclonal
  • Cell Adhesion
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Line
  • DNA / genetics
  • Endothelium, Vascular / immunology
  • Endothelium, Vascular / physiology*
  • Female
  • Fibronectins / metabolism*
  • Flow Cytometry
  • Humans
  • Leukocytes / immunology
  • Leukocytes / physiology*
  • Plasmids
  • Pregnancy
  • Receptors, Fibronectin
  • Receptors, Immunologic / metabolism*
  • Receptors, Very Late Antigen / metabolism*
  • Transfection
  • Umbilical Veins
  • Vascular Cell Adhesion Molecule-1


  • Antibodies, Monoclonal
  • Cell Adhesion Molecules
  • Fibronectins
  • Receptors, Fibronectin
  • Receptors, Immunologic
  • Receptors, Very Late Antigen
  • Vascular Cell Adhesion Molecule-1
  • DNA