Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin.
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.
Shulman
Ziv
Z
Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
Shinder
Vera
V
Klein
Eugenia
E
Grabovsky
Valentin
V
Yeger
Orna
O
Geron
Erez
E
Montresor
Alessio
A
Bolomini-Vittori
Matteo
M
Feigelson
Sara W
SW
Kirchhausen
Tomas
T
Laudanna
Carlo
C
Shakhar
Guy
G
Alon
Ronen
R
D002465:Cell Movement; D002478:Cells, Cultured; D018925:Chemokines / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D018925:Chemokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1