Lymphocyte transcellular migration occurs through recruitment of endothelial ICAM-1 to caveola- and F-actin-rich domains

Nat Cell Biol. 2006 Feb;8(2):113-23. doi: 10.1038/ncb1356. Epub 2006 Jan 22.


During inflammation, leukocytes bind to the adhesion receptors ICAM-1 and VCAM-1 on the endothelial surface before undergoing transendothelial migration, also called diapedesis. ICAM-1 is also involved in transendothelial migration, independently of its role in adhesion, but the molecular basis of this function is poorly understood. Here we demonstrate that, following clustering, apical ICAM-1 translocated to caveolin-rich membrane domains close to the ends of actin stress fibres. In these F-actin-rich areas, ICAM-1 was internalized and transcytosed to the basal plasma membrane through caveolae. Human T-lymphocytes extended pseudopodia into endothelial cells in caveolin- and F-actin-enriched areas, induced local translocation of ICAM-1 and caveolin-1 to the endothelial basal membrane and transmigrated through transcellular passages formed by a ring of F-actin and caveolae. Reduction of caveolin-1 levels using RNA interference (RNAi) specifically decreased lymphocyte transcellular transmigration. We propose that the translocation of ICAM-1 to caveola- and F-actin-rich domains links the sequential steps of lymphocyte adhesion and transendothelial migration and facilitates lymphocyte migration through endothelial cells from capillaries into surrounding tissue.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / metabolism*
  • Antibodies, Monoclonal / pharmacology
  • Caveolae / physiology*
  • Caveolae / ultrastructure
  • Caveolin 1 / genetics
  • Caveolin 1 / metabolism
  • Cell Adhesion / physiology
  • Cell Membrane / metabolism
  • Cell Movement / physiology*
  • Cell Surface Extensions / physiology
  • Cells, Cultured
  • E-Selectin / metabolism
  • Endothelial Cells / cytology
  • Endothelial Cells / drug effects
  • Endothelial Cells / physiology*
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lymphocyte Activation
  • Lymphocytes / cytology
  • Lymphocytes / physiology*
  • Microscopy, Electron, Transmission
  • Microscopy, Fluorescence
  • Protein Transport
  • RNA, Small Interfering / genetics
  • Receptor Aggregation / physiology
  • Stress Fibers / metabolism
  • T-Lymphocytes / cytology
  • T-Lymphocytes / physiology
  • Transfection
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Cell Adhesion Molecule-1 / metabolism


  • Actins
  • Antibodies, Monoclonal
  • CAV1 protein, human
  • Caveolin 1
  • E-Selectin
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1