Nature Immunology6, 497 - 506 (2005)
Published online: 17 April 2005; | doi:10.1038/ni1194
Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines
Revital Shamri1, Valentin Grabovsky1, Jean-Marc Gauguet2, Sara Feigelson1, Eugenia Manevich1, Waldemar Kolanus3, Martyn K Robinson4, Donald E Staunton5, Ulrich H von Andrian2
& Ronen Alon1
1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
CBR Institute for Biomedical Research and the Department of Pathology, Harvard Medical School, Boston Massachusetts 02115, USA.
3
Department of Cellular Biochemistry, Institute of Molecular Physiology and Developmental Biology, University of Bonn, Bonn D-53115, Germany.
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.
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