Cells on the run: shear-regulated integrin activation in leukocyte rolling and arrest on endothelial cells

Curr Opin Cell Biol. 2008 Oct;20(5):525-32. doi: 10.1016/j.ceb.2008.04.003. Epub 2008 May 20.

Abstract

The arrest of rolling leukocytes on various target vascular beds is mediated by specialized leukocyte integrins and their endothelial immunoglobulin superfamily (IgSF) ligands. These integrins are kept in largely inactive states and undergo in situ activation upon leukocyte-endothelial contact by both biochemical and mechanical signals from flow-derived shear forces. In vivo and in vitro studies suggest that leukocyte integrin activation involves conformational alterations through inside-out signaling followed by ligand-induced rearrangements accelerated by external forces. This activation process takes place within fractions of seconds by in situ signals transduced to the rolling leukocyte as it encounters specialized endothelial-displayed chemoattractants, collectively termed arrest chemokines. In neutrophils, selectin rolling engagements trigger intermediate affinity integrins to support reversible adhesions before chemokine-triggered arrest. Different leukocyte subsets appear to use different modalities of integrin activation during rolling and arrest at distinct endothelial sites.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chemokines / metabolism
  • Cytoskeleton / metabolism
  • Endothelial Cells / metabolism*
  • GTP Phosphohydrolases / metabolism
  • Humans
  • Integrins / chemistry
  • Integrins / metabolism*
  • Leukocyte Rolling / physiology*
  • Ligands
  • Lymphocyte Activation / physiology*
  • Models, Molecular
  • Protein Conformation
  • Receptors, G-Protein-Coupled / metabolism
  • Selectins / metabolism
  • Shear Strength
  • Signal Transduction / physiology
  • Stress, Mechanical*

Substances

  • Chemokines
  • Integrins
  • Ligands
  • Receptors, G-Protein-Coupled
  • Selectins
  • GTP Phosphohydrolases