title: Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin.
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.
authors.affiliation: Department of Immunology, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Shulman
authors.forename: Vera
authors.initials: V
authors.lastname: Shinder
authors.forename: Eugenia
authors.initials: E
authors.lastname: Klein
authors.forename: Valentin
authors.initials: V
authors.lastname: Grabovsky
authors.forename: Orna
authors.initials: O
authors.lastname: Yeger
authors.forename: Erez
authors.initials: E
authors.lastname: Geron
authors.forename: Alessio
authors.initials: A
authors.lastname: Montresor
authors.forename: Matteo
authors.initials: M
authors.lastname: Bolomini-Vittori
authors.forename: Sara W
authors.initials: SW
authors.lastname: Feigelson
authors.forename: Tomas
authors.initials: T
authors.lastname: Kirchhausen
authors.forename: Carlo
authors.initials: C
authors.lastname: Laudanna
authors.forename: Guy
authors.initials: G
authors.lastname: Shakhar
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
mesh_terms: 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*
chemical_list: D018925:Chemokines; D016169:Lymphocyte Function-Associated Antigen-1; D018799:Intercellular Adhesion Molecule-1