Human endothelial-cell specific molecule-1 binds directly to the integrin CD11a/CD18 (LFA-1) and blocks binding to intercellular adhesion molecule-1

J Immunol. 2001 Sep 15;167(6):3099-106. doi: 10.4049/jimmunol.167.6.3099.


ICAMs are ligands for LFA-1, a major integrin of mononuclear cells involved in the immune and inflammatory processes. We previously showed that endothelial cell specific molecule-1 (ESM-1) is a proteoglycan secreted by endothelial cells under the control of inflammatory cytokines. Here, we demonstrate that ESM-1 binds directly to LFA-1 onto the cell surface of human blood lymphocytes, monocytes, and Jurkat cells. The binding of ESM-1 was equally dependent on Ca(2+), Mg(2+), or Mn(2+) divalent ions, which are specific, saturable, and sensitive to temperature. An anti-CD11a mAb or PMA induced a transient increase in binding, peaking 5 min after activation. Direct binding of ESM-1 to LFA-1 integrin was demonstrated by specific coimmunoprecipitation by CD11a and CD18 mAbs. A cell-free system using a Biacore biosensor confirmed that ESM-1 and LFA-1 dynamically interacted in real time with high affinity (K(d) = 18.7 nM). ESM-1 consistently inhibited the specific binding of soluble ICAM-1 to Jurkat cells in a dose-dependent manner. These results suggest that ESM-1 and ICAM-1 interact with LFA-1 on binding sites very close to but distinct from the I domain of CD11a. Through this mechanism, ESM-1 could be implicated in the regulation of the LFA-1/ICAM-1 pathway and may therefore influence both the recruitment of circulating lymphocytes to inflammatory sites and LFA-1-dependent leukocyte adhesion and activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques
  • CD18 Antigens / metabolism*
  • Cell Adhesion / physiology
  • Cell Movement / physiology
  • Cell-Free System
  • Computer Systems
  • Endothelium, Vascular / physiology*
  • Humans
  • Inflammation
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Jurkat Cells / metabolism
  • Lymphocyte Activation / physiology
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Neoplasm Proteins*
  • Protein Binding / drug effects
  • Protein Structure, Tertiary
  • Proteins / metabolism*
  • Proteins / pharmacology
  • Proteoglycans*
  • Temperature
  • Tetradecanoylphorbol Acetate / pharmacology


  • CD18 Antigens
  • ESM1 protein, human
  • Lymphocyte Function-Associated Antigen-1
  • Neoplasm Proteins
  • Proteins
  • Proteoglycans
  • Intercellular Adhesion Molecule-1
  • Tetradecanoylphorbol Acetate