Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin

Immunity. 2009 Mar 20;30(3):384-96. doi: 10.1016/j.immuni.2008.12.020. Epub 2009 Mar 5.

Abstract

Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte integrins to support shear-resistant motility on and across cytokine-stimulated endothelial barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes. Shear forces applied to endothelial-bound lymphocytes dramatically enhanced filopodia density underneath crawling lymphocytes. A fraction of the adhesive filopodia invaded the endothelial cells prior to and during TEM and extended large subluminal leading edge containing dots of HA-LFA-1 occupied by subluminal ICAM-1. Memory T cells generated more frequent invasive filopodia and transmigrated more rapidly than their naive counterparts. We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Movement*
  • Cells, Cultured
  • Chemokines / immunology*
  • Endothelium, Vascular / immunology*
  • Humans
  • Intercellular Adhesion Molecule-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / immunology*
  • T-Lymphocytes / immunology*

Substances

  • Chemokines
  • Lymphocyte Function-Associated Antigen-1
  • Intercellular Adhesion Molecule-1