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Transendothelial migration of lymphocytes mediated by intraendothelial vesicle stores rather than by extracellular chemokine depots

Shulman, Ziv
Cohen, Shmuel J
Roediger, Ben
Kalchenko, Vyacheslav
Jain, Rohit
Grabovsky, Valentin
Klein, Eugenia
Shinder, Vera
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Published in Nature Immunology. 2012, vol. 13, no. 1, p. 67-76
Abstract Chemokines presented by the endothelium are critical for integrin-dependent adhesion and transendothelial migration of naive and memory lymphocytes. Here we found that effector lymphocytes of the type 1 helper T cell (T(H)1 cell) and type 1 cytotoxic T cell (T(C)1 cell) subtypes expressed adhesive integrins that bypassed chemokine signals and established firm arrests on variably inflamed endothelial barriers. Nevertheless, the transendothelial migration of these lymphocytes strictly depended on signals from guanine nucleotide-binding proteins of the G(i) type and was promoted by multiple endothelium-derived inflammatory chemokines, even without outer endothelial surface exposure. Instead, transendothelial migration-promoting endothelial chemokines were stored in vesicles docked on actin fibers beneath the plasma membranes and were locally released within tight lymphocyte-endothelial synapses. Thus, effector T lymphocytes can cross inflamed barriers through contact-guided consumption of intraendothelial chemokines without surface-deposited chemokines or extraendothelial chemokine gradients.
Keywords AnimalsAntigens, CD44/metabolismCell Membrane/metabolismCells, CulturedChemokines/metabolismEndothelial Cells/drug effects/metabolismGTP-Binding Protein alpha Subunits, Gi-Go/metabolismHumansIntegrins/metabolismLymphocytes/immunology/metabolism/ultrastructureMiceReceptors, CCR2/metabolismSignal TransductionT-Lymphocytes/immunology/metabolism/ultrastructureTransendothelial and Transepithelial Migration/immunologyTransport Vesicles/metabolismTumor Necrosis Factor-alpha/pharmacologyVasculitis/immunology/metabolism
PMID: 22138716
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SHULMAN, Ziv et al. Transendothelial migration of lymphocytes mediated by intraendothelial vesicle stores rather than by extracellular chemokine depots. In: Nature Immunology, 2012, vol. 13, n° 1, p. 67-76. doi: 10.1038/ni.2173 https://archive-ouverte.unige.ch/unige:23659

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Deposited on : 2012-11-01

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