title: Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines.
abstract: It is widely believed that rolling lymphocytes require successive chemokine-induced signaling for lymphocyte function-associated antigen 1 (LFA-1) to achieve a threshold avidity that will mediate lymphocyte arrest. Using an in vivo model of lymphocyte arrest, we show here that LFA-1-mediated arrest of lymphocytes rolling on high endothelial venules bearing LFA-1 ligands and chemokines was abrupt. In vitro flow chamber models showed that endothelium-presented but not soluble chemokines triggered instantaneous extension of bent LFA-1 in the absence of LFA-1 ligand engagement. To support lymphocyte adhesion, this extended LFA-1 conformation required immediate activation by its ligand, intercellular adhesion molecule 1. These data show that chemokine-triggered lymphocyte adhesiveness involves a previously unrecognized extension step that primes LFA-1 for ligand binding and firm adhesion.
authors.affiliation: Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Revital
authors.initials: R
authors.lastname: Shamri
authors.forename: Valentin
authors.initials: V
authors.lastname: Grabovsky
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Gauguet
authors.forename: Sara
authors.initials: S
authors.lastname: Feigelson
authors.forename: Eugenia
authors.initials: E
authors.lastname: Manevich
authors.forename: Waldemar
authors.initials: W
authors.lastname: Kolanus
authors.forename: Martyn K
authors.initials: MK
authors.lastname: Robinson
authors.forename: Donald E
authors.initials: DE
authors.lastname: Staunton
authors.forename: Ulrich H
authors.initials: UH
authors.lastname: von Andrian
authors.forename: Ronen
authors.initials: R
authors.lastname: Alon
mesh_terms: D000494:Allosteric Regulation; D002448:Cell Adhesion; D002478:Cells, Cultured; D018925:Chemokines / Q000378:metabolism* / Q000494:pharmacology; D003599:Cytoskeleton / Q000378:metabolism; D004727:Endothelium / Q000378:metabolism*; D000939:Epitopes / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D011487:Protein Conformation / Q000187:drug effects; D021122:Protein Subunits / Q000276:immunology / Q000378:metabolism; D012995:Solubility; D016608:Talin / Q000378:metabolism
chemical_list: D018925:Chemokines; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D021122:Protein Subunits; D016608:Talin; D018799:Intercellular Adhesion Molecule-1