Filamin B mediates ICAM-1-driven leukocyte transendothelial migration

J Biol Chem. 2008 Nov 14;283(46):31830-9. doi: 10.1074/jbc.M804888200. Epub 2008 Sep 22.


During inflammation, the endothelium mediates rolling and firm adhesion of activated leukocytes. Integrin-mediated adhesion to endothelial ligands of the Ig-superfamily induces intracellular signaling in endothelial cells, which promotes leukocyte transendothelial migration. We identified the actin cross-linking molecule filamin B as a novel binding partner for intracellular adhesion molecule-1 (ICAM-1). Immune precipitation as well as laser scanning confocal microscopy confirmed the specific interaction and co-localization of endogenous filamin B with ICAM-1. Importantly, clustering of ICAM-1 promotes the ICAM-1-filamin B interaction. To investigate the functional consequences of filamin B binding to ICAM-1, we used small interfering RNA to reduce filamin B expression in ICAM-1-GFP expressing HeLa cells. We found that filamin B is required for the lateral mobility of ICAM-1 and for ICAM-1-induced transmigration of leukocytes. Reducing filamin B expression in primary human endothelial cells resulted in reduced recruitment of ICAM-1 to endothelial docking structures, reduced firm adhesion of the leukocytes to the endothelium, and inhibition of transendothelial migration. In conclusion, this study identifies filamin B as a molecular linker that mediates ICAM-1-driven transendothelial migration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caveolin 1 / metabolism
  • Cell Movement*
  • Cells, Cultured
  • Chlorocebus aethiops
  • Contractile Proteins / genetics
  • Contractile Proteins / metabolism*
  • Endothelial Cells / cytology*
  • Endothelial Cells / metabolism*
  • Filamins
  • Genes, Reporter / genetics
  • Humans
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Leukocytes / cytology*
  • Leukocytes / metabolism*
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Protein Binding


  • Caveolin 1
  • Contractile Proteins
  • Filamins
  • Microfilament Proteins
  • Intercellular Adhesion Molecule-1