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J. Biol. Chem., Vol. 280, Issue 52, 43079-43086, December 30, 2005
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1
2





3
From the
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 and the
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, Wisconsin 53226
Docosahexaenoic acid, a major
-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
and interferon-
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.
Received for publication, September 7, 2005 , and in revised form, October 5, 2005.
* This work was supported in part by Grants GM38765, P01-DE13499, and P50-DE016191 (to C. N. S.) from the National Institutes of Health. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 Recipient of the 2003 McDuffie postdoctoral fellowship award from the Arthritis Foundation.
2 Performed this work while on a sabbatical leave from the Medical College of Wisconsin. Present address: Dept. of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298.
3 To whom correspondence should be addressed: Center for Experimental Therapeutics and Reperfusion Injury, Dept. of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115. Tel.: 617-732-8822; Fax: 617-582-6141; E-mail: cnserhan{at}zeus.bwh.harvard.edu.
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