The docosatriene protectin D1 is produced by TH2 skewing and promotes human T cell apoptosis via lipid raft clustering.
Docosahexaenoic acid, a major omega-3 fatty acid in human brain, synapses, retina, and other neural tissues, displays beneficial actions in neuronal development, cancer, and inflammatory diseases by mechanisms that remain to be elucidated. In this study we found, using lipid mediator informatics employing liquid chromatography-tandem mass spectrometry, that (10,17S)-docosatriene/neuroprotectin D1, now termed protectin D1 (PD1), is generated from docosahexaenoic acid by T helper type 2-skewed peripheral blood mononuclear cells in a lipoxygenase-dependent manner. PD1 blocked T cell migration in vivo, inhibited tumor necrosis factor alpha and interferon-gamma secretion, and promoted apoptosis mediated by raft clustering. These results demonstrated novel anti-inflammatory roles for PD1 in regulating events associated with inflammation and resolution.
Ariel
Amiram
A
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.
Li
Pin-Lan
PL
Wang
Wei
W
Tang
Wang-Xian
WX
Fredman
Gabrielle
G
Hong
Song
S
Gotlinger
Katherine H
KH
Serhan
Charles N
CN
D000818:Animals; D017209:Apoptosis; D001093:Arachidonate 15-Lipoxygenase / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002853:Chromatography, Liquid; D016207:Cytokines / Q000378:metabolism; D004281:Docosahexaenoic Acids / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D007371:Interferon-gamma / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D013058:Mass Spectrometry; D021962:Membrane Microdomains / Q000737:chemistry*; D051379:Mice; D008956:Models, Chemical; D018384:Oxidative Stress; D010538:Peritonitis / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015054:Zymosan / Q000737:chemistry
D016207:Cytokines; D014409:Tumor Necrosis Factor-alpha; C487679:protectin D1; D004281:Docosahexaenoic Acids; D007371:Interferon-gamma; D015054:Zymosan; D001093:Arachidonate 15-Lipoxygenase