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.
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Acknowledgements
We thank S. Schwarzbaum for editorial help. Supported by the German-Israeli Foundation for Scientific Research and Development, the Israel Science Foundation and MAIN, the EU6 Program for Migration and Inflammation.
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Supplementary information
Supplementary Fig. 1
Instantaneous rolling velocities of 11 lymphocytes (cells a-k). (PDF 377 kb)
Supplementary Fig. 2
Immobilized but not soluble SDF-1 triggers instantaneous LFA-1 activation on lymphocytes tethered to and rolling on an inflamed endothelial surface. (PDF 106 kb)
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Shamri, R., Grabovsky, V., Gauguet, JM. et al. Lymphocyte arrest requires instantaneous induction of an extended LFA-1 conformation mediated by endothelium-bound chemokines. Nat Immunol 6, 497–506 (2005). https://doi.org/10.1038/ni1194
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DOI: https://doi.org/10.1038/ni1194
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