Source:http://linkedlifedata.com/resource/pubmed/id/15060082
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
24
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pubmed:dateCreated |
2004-6-7
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pubmed:abstractText |
Interactions between CD44 and hyaluronan are implicated in the primary adhesion of lymphocytes to endothelium at inflammatory locations. Here we show that preincubation of hyaluronan with full-length recombinant TSG-6 or its Link module domain (Link_TSG6) enhances or induces the binding of hyaluronan to cell surface CD44 on constitutive and inducible cell backgrounds, respectively. These effects are blocked by CD44-specific antibodies and are absent in CD44-negative cells. Enhancement of CD44-mediated interactions of lymphoid cells with hyaluronan by TSG-6 proteins was seen under conditions of flow at shear forces that occur in post-capillary venules. Increases in the number of rolling cells were observed on substrates comprising TSG-6-hyaluronan complexes as compared with a substrate containing hyaluronan alone. In ligand competition experiments, cell surface-bound TSG-6-hyaluronan complexes were more potent than hyaluronan alone in inhibiting cell adhesion to immobilized hyaluronan. Link_TSG6 mutants with impaired hyaluronan binding function had a reduced ability to modulate ligand binding by cell surface CD44. However, some mutants that exhibited close to wild-type hyaluronan binding were found to have either reduced or increased activity, suggesting that some amino acid residues outside of the hyaluronan binding site might be involved in protein self-association, potentially leading to the formation of cross-linked hyaluronan fibers. In turn, cross-linked hyaluronan could increase the binding avidity of CD44 by inducing receptor clustering. The ability of TSG-6 to modulate the interaction of hyaluronan with CD44 has important implications for CD44-mediated cell activity at sites of inflammation, where TSG-6 is expressed.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
279
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
25745-54
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15060082-Animals,
pubmed-meshheading:15060082-Antigens, CD44,
pubmed-meshheading:15060082-Cell Adhesion,
pubmed-meshheading:15060082-Cell Adhesion Molecules,
pubmed-meshheading:15060082-Cell Line, Tumor,
pubmed-meshheading:15060082-Cell Movement,
pubmed-meshheading:15060082-Hyaluronic Acid,
pubmed-meshheading:15060082-Mice,
pubmed-meshheading:15060082-Mice, Inbred AKR
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pubmed:year |
2004
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pubmed:articleTitle |
TSG-6 modulates the interaction between hyaluronan and cell surface CD44.
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pubmed:affiliation |
Molecular and Cell Biology Laboratory, The Salk Institute, San Diego, California 92186, 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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