Chemokines trigger immediate beta2 integrin affinity and mobility changes: differential regulation and roles in lymphocyte arrest under flow

Immunity. 2000 Dec;13(6):759-69. doi: 10.1016/s1074-7613(00)00074-1.


Chemokines trigger rapid integrin-dependent lymphocyte arrest to vascular endothelium. We show that the chemokines SLC, ELC, and SDF-1alpha rapidly induce lateral mobility and transient increase of affinity of the beta2 integrin LFA-1. Inhibition of phosphatidylinositol 3-OH kinase (PI(3)K) activity blocks mobility but not affinity changes and prevents lymphocyte adhesion to ICAM-1 immobilized at low but not high densities, suggesting that mobility enhances the frequency of encounters between high-affinity integrin and ligand but that at higher ligand density affinity changes are sufficient for arrest. Thus, chemokines trigger, through distinct signaling pathways, both a high-affinity state and lateral mobility of LFA-1 that can coordinately determine the vascular arrest of circulating lymphocytes under physiologic conditions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • CD18 Antigens / metabolism
  • Cell Adhesion
  • Cell Membrane / metabolism
  • Cell Movement / physiology*
  • Cells, Cultured
  • Chemokine CCL19
  • Chemokine CCL21
  • Chemokine CXCL12
  • Chemokines, CC / metabolism*
  • Chemokines, CC / pharmacology
  • Chemokines, CXC / metabolism*
  • Chemokines, CXC / pharmacology
  • Endopeptidases / metabolism
  • Endothelium, Vascular / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Lymphocytes / cytology
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Lymphocytes / physiology*
  • Mice
  • Models, Biological
  • Peyer's Patches / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Time Factors


  • CCL19 protein, human
  • CCL21 protein, human
  • CD18 Antigens
  • CXCL12 protein, human
  • Ccl19 protein, mouse
  • Ccl21c protein, mouse
  • Chemokine CCL19
  • Chemokine CCL21
  • Chemokine CXCL12
  • Chemokines, CC
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1
  • Phosphatidylinositol 3-Kinases
  • Endopeptidases