Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines.
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.
Shamri
Revital
R
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
Grabovsky
Valentin
V
Gauguet
Jean-Marc
JM
Feigelson
Sara
S
Manevich
Eugenia
E
Kolanus
Waldemar
W
Robinson
Martyn K
MK
Staunton
Donald E
DE
von Andrian
Ulrich H
UH
Alon
Ronen
R
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
D018925:Chemokines; D000939:Epitopes; D016169:Lymphocyte Function-Associated Antigen-1; D021122:Protein Subunits; D016608:Talin; D018799:Intercellular Adhesion Molecule-1