Shear forces promote lymphocyte migration across vascular endothelium bearing apical chemokines

Nat Immunol. 2001 Jun;2(6):515-22. doi: 10.1038/88710.


Leukocyte transendothelial migration (TEM) is thought to be a chemotactic process controlled by chemokine gradients across the endothelium. Using cytokine-activated human umbilical vascular endothelial cells (HUVECs) as a model of inflamed endothelium, we have shown that apical endothelial chemokines can trigger robust peripheral blood lymphocyte (PBL) migration across endothelial cells. Lymphocyte TEM was promoted by physiological shear stress applied continuously to migrating lymphocytes. Lymphocyte integrins, intact actin cytoskeleton and G(i) protein-mediated chemokine signaling, but not a chemotactic gradient, were mandatory for TEM. PBL TEM did not require intracellular free calcium or intact phosphatidyl inositol kinase activity in migrating lymphocytes. Thus, lymphocyte TEM is promoted by fluid shear-induced mechanical signals coupled to G(i) protein signals at apical endothelial zones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Movement / immunology*
  • Cell Movement / physiology*
  • Cells, Cultured
  • Chemokines / physiology*
  • Chemotaxis, Leukocyte / immunology
  • Chemotaxis, Leukocyte / physiology
  • Cricetinae
  • Endothelium, Vascular / cytology*
  • Endothelium, Vascular / immunology*
  • GTP-Binding Proteins / physiology
  • Humans
  • In Vitro Techniques
  • Integrins / physiology
  • Lymphocytes / immunology*
  • Lymphocytes / physiology*
  • Lymphocytes / ultrastructure
  • Microscopy, Electron
  • Permeability
  • Signal Transduction
  • Stress, Mechanical


  • Chemokines
  • Integrins
  • GTP-Binding Proteins