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 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.
Hong
Song
S
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Gronert
Karsten
K
Devchand
Pallavi R
PR
Moussignac
Rose-Laure
RL
Serhan
Charles N
CN
D000818:Animals; D001769:Blood / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D016207:Cytokines / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000378:metabolism*; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D009457:Neuroglia / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D005231:Fatty Acids, Unsaturated; D014409:Tumor Necrosis Factor-alpha; D004281:Docosahexaenoic Acids