Source:http://linkedlifedata.com/resource/pubmed/id/17346796
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2007-4-20
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pubmed:abstractText |
The pathways regulating integrin-mediated adhesion during neutrophil migration are incompletely defined. Using a flow-based model in which human neutrophils rolling on P-selectin were activated to migrate by the chemoattractant peptide fMLP, we investigated the role of phospholipase D (PLD). fMLP-stimulated PLD generation of phosphatidate (PtdOH); while inhibition of PtdOH production with butan-1-ol had no effect on the initial immobilisation of rolling neutrophils (supported by activation of constitutively surface-expressed beta(2)-integrin CD11b/CD18) it impaired longer-term stability of adhesion and reduced the rate of migration (supported by activation of de novo-exocytosed CD11b/CD18). PtdOH regulated these processes by controlling activation of exocytosed CD11b/CD18, and appeared to act by directly stimulating phosphatidylinositol 4-phosphate 5-kinase type I to generate phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P(2)). Cell-permeable PtdIns(4,5)P(2) recovered migration of neutrophils after PLD inhibition; PtdIns(4,5)P(2) appeared to act by promoting talin binding to CD18 and hence activating CD11b/CD18, as migration was inhibited when neutrophils were loaded with peptides previously shown to block the interaction between PtdIns(4,5)P(2) and talin or talin and CD18. Thus, these data indicate that PLD-synthesised PtdOH stimulates the generation of PtdIns(4,5)P(2), which in turn mediates talin binding to, and activation of, CD11b/CD18 required for neutrophil stable adhesion and migration.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD11b,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD18,
http://linkedlifedata.com/resource/pubmed/chemical/ITGAM protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Integrins,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphatidic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipase D
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0161-5890
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
44
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3211-21
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pubmed:dateRevised |
2007-8-13
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pubmed:meshHeading |
pubmed-meshheading:17346796-Antigens, CD11b,
pubmed-meshheading:17346796-Antigens, CD18,
pubmed-meshheading:17346796-Cell Adhesion,
pubmed-meshheading:17346796-Chemotaxis, Leukocyte,
pubmed-meshheading:17346796-Humans,
pubmed-meshheading:17346796-Integrins,
pubmed-meshheading:17346796-Leukocyte Rolling,
pubmed-meshheading:17346796-Neutrophils,
pubmed-meshheading:17346796-Phosphatidic Acids,
pubmed-meshheading:17346796-Phospholipase D
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pubmed:year |
2007
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pubmed:articleTitle |
Stable adhesion and migration of human neutrophils requires phospholipase D-mediated activation of the integrin CD11b/CD18.
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pubmed:affiliation |
CRUK Institute for Cancer Studies, The Medical School, The University of Birmingham, Birmingham, B15 2TT, UK. D.J.Powner.20@bham.ac.uk <D.J.Powner.20@bham.ac.uk>
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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