Source:http://linkedlifedata.com/resource/pubmed/id/11739530
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2001-12-12
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| pubmed:abstractText |
Chemokine receptors are rapidly desensitized and internalized following ligand binding, a process that attenuates receptor-mediated responses. However, the physiological settings in which this process occurs are not clear. Therefore, we examined the fate of CXCR3, a chemokine receptor preferentially expressed on activated T cells following contact with endothelial cells. By immunofluorescence microscopy and flow cytometry, we found that CXCR3 was rapidly internalized when T cells were incubated with IFN-gamma-activated human saphenous vein endothelial cells (HSVEC), but not with resting HSVEC. Similar results were obtained using human CXCR3-transfected murine 300-19 B cells. CXCR3 down-regulation was significantly more pronounced when T cells were in contact with HSVEC than with their supernatants, suggesting that CXCR3 ligands were efficiently displayed on the surface of HSVEC. Using neutralizing mAbs to IFN-induced protein-10 (CXCL10), monokine induced by IFN-gamma (CXCL9), and IFN-inducible T cell alpha chemoattractant (I-TAC; CXCL11), we found that even though I-TAC was secreted from IFN-gamma-activated HSVEC to lower levels than IFN-induced protein-10 or the monokine induced by IFN-gamma, it was the principal chemokine responsible for CXCR3 internalization. This correlated with studies using recombinant chemokines, which revealed that I-TAC was the most potent inducer of CXCR3 down-regulation and of transendothelial migration. Known inhibitors of chemokine-induced chemotaxis, such as pertussis toxin or wortmannin, did not reduce ligand-induced internalization, suggesting that a distinct signal transduction pathway mediates internalization. Our data demonstrate that I-TAC is the physiological inducer of CXCR3 internalization and suggest that chemokine receptor internalization occurs in physiological settings, such as leukocyte contact with an activated endothelium.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
AIM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CXCL11 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CXCL9 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/CXCR3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL10,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL11,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokine CXCL9,
http://linkedlifedata.com/resource/pubmed/chemical/Chemokines, CXC,
http://linkedlifedata.com/resource/pubmed/chemical/Culture Media, Conditioned,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin,
http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, CXCR3,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Chemokine
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
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| pubmed:issn |
0022-1767
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
15
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| pubmed:volume |
167
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
7084-93
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| pubmed:dateRevised |
2008-11-21
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| pubmed:meshHeading |
pubmed-meshheading:11739530-Cell Adhesion,
pubmed-meshheading:11739530-Cells, Cultured,
pubmed-meshheading:11739530-Chemokine CXCL10,
pubmed-meshheading:11739530-Chemokine CXCL11,
pubmed-meshheading:11739530-Chemokine CXCL9,
pubmed-meshheading:11739530-Chemokines, CXC,
pubmed-meshheading:11739530-Chemotaxis, Leukocyte,
pubmed-meshheading:11739530-Culture Media, Conditioned,
pubmed-meshheading:11739530-Down-Regulation,
pubmed-meshheading:11739530-Endocytosis,
pubmed-meshheading:11739530-Endothelium, Vascular,
pubmed-meshheading:11739530-Heparin,
pubmed-meshheading:11739530-Humans,
pubmed-meshheading:11739530-Intercellular Signaling Peptides and Proteins,
pubmed-meshheading:11739530-Interferon-gamma,
pubmed-meshheading:11739530-Kinetics,
pubmed-meshheading:11739530-Microscopy, Fluorescence,
pubmed-meshheading:11739530-Protein Transport,
pubmed-meshheading:11739530-Receptors, CXCR3,
pubmed-meshheading:11739530-Receptors, Chemokine,
pubmed-meshheading:11739530-T-Lymphocytes
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| pubmed:year |
2001
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| pubmed:articleTitle |
CXCR3 internalization following T cell-endothelial cell contact: preferential role of IFN-inducible T cell alpha chemoattractant (CXCL11).
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| pubmed:affiliation |
Division of Rheumatology, Allergy, and Immunology, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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