The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
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Published online December 22, 2008
doi:10.1084/jem.20081880
The Journal of Experimental Medicine
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Serhan et al.
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BRIEF DEFINITIVE REPORT

 Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions

Charles N. Serhan, Rong Yang, Kimberly Martinod, Kie Kasuga, Padmini S. Pillai, Timothy F. Porter, Sungwhan F. Oh, and Matthew Spite

Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115

CORRESPONDENCE Charles N. Serhan: cnserhan{at}zeus.bwh.harvard.edu

The endogenous cellular and molecular mechanisms that control acute inflammation and its resolution are of wide interest. Using self-resolving inflammatory exudates and lipidomics, we have identified a new pathway involving biosynthesis of potent antiinflammatory and proresolving mediators from the essential fatty acid docosahexaenoic acid (DHA) by macrophages (M{Phi}s). During the resolution of mouse peritonitis, exudates accumulated both 17-hydroxydocosahexaenoic acid, a known marker of 17S-D series resolvin (Rv) and protectin biosynthesis, and 14S-hydroxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid from endogenous DHA. Addition of either DHA or 14S-hydroperoxydocosa-4Z,7Z,10Z,12E,16Z,19Z-hexaenoic acid to activated M{Phi}s converted these substrates to novel dihydroxy-containing products that possessed potent antiinflammatory and proresolving activity with a potency similar to resolvin E1, 5S,12R,18R-trihydroxyeicosa-6Z,8E,10E,14Z,16E-pentaenoic acid, and protectin D1, 10R,17S-dihydroxydocosa-4Z,7Z,11E,13E,15Z,19Z-hexaenoic acid. Stable isotope incorporation, intermediate trapping, and characterization of physical and biological properties of the products demonstrated a novel 14-lipoxygenase pathway, generating bioactive 7,14-dihydroxydocosa-4Z,8,10,12,16Z,19Z-hexaenoic acid, coined M{Phi} mediator in resolving inflammation (maresin), which enhances resolution. These findings suggest that maresins and this new metabolome may be involved in some of the beneficial actions of DHA and M{Phi}s in tissue homeostasis, inflammation resolution, wound healing, and host defense.

© 2009 Serhan et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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