Novel docosatrienes and 17S-resolvins generated from docosahexaenoic acid in murine brain, human blood, and glial cells. Autacoids in anti-inflammation

Docosahexaenoic acid (DHA, C22:6) is highly enriched in brain, synapses, and retina and is a major omega-3 fatty acid. Deficiencies in this essential fatty acid are reportedly associated with neuronal function, cancer, and inflammation. Here, using new lipidomic analyses employing high performance l...

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Bibliographic Details
Published in:The Journal of biological chemistry 2003-04, Vol.278 (17), p.14677-14687
Main Authors: Hong, Song, Gronert, Karsten, Devchand, Pallavi R, Moussignac, Rose-Laure, Serhan, Charles N
Format: Article
Language:English
Subjects:
Animals
Blood - metabolism
Brain - metabolism
Chemotaxis, Leukocyte - drug effects
Chromatography, High Pressure Liquid
Cytokines - biosynthesis
Docosahexaenoic acid
Docosahexaenoic Acids - metabolism
Fatty Acids, Unsaturated - metabolism
Humans
Inflammation
Leukocytes - metabolism
Mass Spectrometry
Mice
Neuroglia - metabolism
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Docosahexaenoic acid (DHA, C22:6) is highly enriched in brain, synapses, and retina and is a major omega-3 fatty acid. Deficiencies in this essential fatty acid are reportedly associated with neuronal function, cancer, and inflammation. Here, using new lipidomic analyses employing high performance liquid chromatography coupled with a photodiode-array detector and a tandem mass spectrometer, a novel series of endogenous mediators was identified in blood, leukocytes, brain, and glial cells as 17S-hydroxy-containing docosanoids denoted as docosatrienes (the main bioactive member of the series was 10,17S-docosatriene) and 17S series resolvins. These novel mediators were biosynthesized via epoxide-containing intermediates and proved potent (pico- to nanomolar range) regulators of both leukocytes reducing infiltration in vivo and glial cells blocking their cytokine production. These results indicate that DHA is the precursor to potent protective mediators generated via enzymatic oxygenations to novel docosatrienes and 17S series resolvins that each regulate events of interest in inflammation and resolution.
ISSN:0021-9258
DOI:10.1074/jbc.M300218200