Source:http://linkedlifedata.com/resource/pubmed/id/16495221
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
15
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| pubmed:dateCreated |
2006-4-10
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| pubmed:abstractText |
Priming of human neutrophils with granulocyte-macrophage colony-stimulating factor (GM-CSF) followed by treatment with formyl-methionyl-leucyl-phenylalanine (fMLP) stimulates cells in a physiologically relevant manner with modest 5-lipoxygenase activation and formation of leukotrienes. However, pretreatment of neutrophils with thimerosal, an organomercury thiosalicylic acid derivative, led to a dramatic increase (>50-fold) in the production of leukotriene B(4) and 5-hydroxyeicosatetraenoic acid, significantly higher than that observed after stimulation with calcium ionophore A23187. Little or no effect was observed with thimerosal alone or in combination with either GM-CSF or fMLP. Elevation of [Ca(2+)](i) induced by thimerosal in neutrophils stimulated with GM-CSF/fMLP was similar but more sustained compared with samples where thimerosal was absent. However, [Ca(2+)](i) was significantly lower compared with calcium ionophore-treated cells, suggesting that a sustained calcium rise was necessary but not sufficient to explain the effects of this compound on the GM-CSF/fMLP-stimulated neutrophil. Thimerosal was found to directly inhibit neutrophil lysophospholipid:acyl-CoA acyltransferase activity at the doses that stimulate leukotriene production, and analysis of lysates from neutrophil preparations stimulated in the presence of thimerosal showed a marked increase in free arachidonic acid, supporting the inhibition of the reincorporation of this fatty acid into the membrane phospholipids as a mechanism of action for this compound. The dramatic increase in production of leukotrienes by neutrophils when a physiological stimulus such as GM-CSF/fMLP is employed in the presence of thimerosal suggests a critical regulatory role of arachidonate reacylation that limits leukotriene biosynthesis in concert with 5-lipoxygenase and cytosolic phospholipase A(2)alpha activation.
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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/5-hydroxy-6,8,11,14-eicosatetraenoic...,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonate 5-Lipoxygenase,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Calcimycin,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium,
http://linkedlifedata.com/resource/pubmed/chemical/Granulocyte-Macrophage...,
http://linkedlifedata.com/resource/pubmed/chemical/Group IV Phospholipases A2,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyeicosatetraenoic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Ionophores,
http://linkedlifedata.com/resource/pubmed/chemical/Leukotrienes,
http://linkedlifedata.com/resource/pubmed/chemical/N-Formylmethionine...,
http://linkedlifedata.com/resource/pubmed/chemical/Phospholipases A,
http://linkedlifedata.com/resource/pubmed/chemical/Thimerosal
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Apr
|
| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
14
|
| pubmed:volume |
281
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
10134-42
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| pubmed:dateRevised |
2007-11-15
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| pubmed:meshHeading |
pubmed-meshheading:16495221-Arachidonate 5-Lipoxygenase,
pubmed-meshheading:16495221-Arachidonic Acid,
pubmed-meshheading:16495221-Calcimycin,
pubmed-meshheading:16495221-Calcium,
pubmed-meshheading:16495221-Cytosol,
pubmed-meshheading:16495221-Dose-Response Relationship, Drug,
pubmed-meshheading:16495221-Enzyme Activation,
pubmed-meshheading:16495221-Gas Chromatography-Mass Spectrometry,
pubmed-meshheading:16495221-Granulocyte-Macrophage Colony-Stimulating Factor,
pubmed-meshheading:16495221-Group IV Phospholipases A2,
pubmed-meshheading:16495221-Humans,
pubmed-meshheading:16495221-Hydroxyeicosatetraenoic Acids,
pubmed-meshheading:16495221-Ionophores,
pubmed-meshheading:16495221-Leukotrienes,
pubmed-meshheading:16495221-Mass Spectrometry,
pubmed-meshheading:16495221-N-Formylmethionine Leucyl-Phenylalanine,
pubmed-meshheading:16495221-Neutrophils,
pubmed-meshheading:16495221-Phospholipases A,
pubmed-meshheading:16495221-Thimerosal,
pubmed-meshheading:16495221-Time Factors
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| pubmed:year |
2006
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| pubmed:articleTitle |
Effect of arachidonic acid reacylation on leukotriene biosynthesis in human neutrophils stimulated with granulocyte-macrophage colony-stimulating factor and formyl-methionyl-leucyl-phenylalanine.
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| pubmed:affiliation |
Department of Pharmacology, University of Colorado at Denver and Health Sciences Center, 12801 E. 17th Avenue, Aurora, CO 80045, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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