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PMID: 22138716 Published · epublish English Journal Article Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 13 ·No. 1 ·2011-12-04 ·Pages 67-76

Shulman Z, Cohen SJ, Roediger B, Kalchenko V, Jain R, Grabovsky V, Klein E, Shinder V, Stoler-Barak L, Feigelson SW, Meshel T, Nurmi SM, Goldstein I, Hartley O, Gahmberg CG, Etzioni A, Weninger W, Ben-Baruch A, Alon R

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.

MeSH Terms
Animals Cell Membrane/metabolism Cells, Cultured Chemokines/metabolism Endothelial Cells/drug effects,metabolism GTP-Binding Protein alpha Subunits, Gi-Go/metabolism Humans Hyaluronan Receptors/metabolism Integrins/metabolism Lymphocytes/immunology,metabolism,ultrastructure Mice Receptors, CCR2/metabolism Signal Transduction T-Lymphocytes/immunology,metabolism,ultrastructure Transendothelial and Transepithelial Migration/immunology Transport Vesicles/metabolism Tumor Necrosis Factor-alpha/pharmacology Vasculitis/immunology,metabolism
Chemicals
Chemokines Hyaluronan Receptors Integrins Receptors, CCR2 Tumor Necrosis Factor-alpha GTP-Binding Protein alpha Subunits, Gi-Go
Authors & Affiliations
19 authors, click to expand affiliations / ORCID
Shulman Ziv
Department of Immunology, Weizmann Institute of Science, Rehovot, Israel.
Cohen Shmuel J
Roediger Ben
Kalchenko Vyacheslav
Jain Rohit
Grabovsky Valentin
Klein Eugenia
Shinder Vera
Stoler-Barak Liat
Feigelson Sara W
Meshel Tsipi
Nurmi Susanna M
Goldstein Itamar
Hartley Olivier
Gahmberg Carl G
Etzioni Amos
Weninger Wolfgang
Ben-Baruch Adit
Alon Ronen
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.2173
Published
2011-12-04
Epub
2011-00-04
Pages
67-76
Language
English
Region
United States
NLM ID
100941354
Subset
IM
Corrections
CommentIn
PMID: 22179273
CommentIn
PMID: 22207305
External Links
PubMed source DOI: 10.1038/ni.2173 View journal details
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