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Front. Immunol., 17 April 2012 |

Functional metabolomics reveals novel active products in the DHA metabolome

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

Endogenous mechanisms for successful resolution of an acute inflammatory response and the local return to homeostasis are of interest because excessive inflammation underlies many human diseases. In this review, we provide an update and overview of functional metabolomics that identified a new bioactive metabolome of docosahexaenoic acid (DHA). Systematic studies revealed that DHA was converted to DHEA-derived novel bioactive products as well as aspirin-triggered forms of protectins (AT-PD1). The new oxygenated DHEA-derived products blocked PMN chemotaxis, reduced P-selectin expression and platelet-leukocyte adhesion, and showed organ protection in ischemia/reperfusion injury. These products activated cannabinoid receptor (CB2 receptor) and not CB1 receptors. The AT-PD1 reduced neutrophil (PMN) recruitment in murine peritonitis. With human cells, AT-PD1 decreased transendothelial PMN migration as well as enhanced efferocytosis of apoptotic human PMN by macrophages. The recent findings reviewed here indicate that DHEA oxidative metabolism and aspirin-triggered conversion of DHA produce potent novel molecules with anti-inflammatory and organ-protective properties, opening the DHA metabolome functional roles.

Keywords: resolvins, protectins, specialized pro-resolving mediator, DHEA, neutrophil, aspirin

Citation: Shinohara M, Mirakaj V and Serhan CN (2012) Functional metabolomics reveals novel active products in the DHA metabolome. Front. Immun. 3:81. doi: 10.3389/fimmu.2012.00081

Received: 07 February 2012; Paper pending published: 21 February 2012;
Accepted: 29 March 2012; Published online: 17 April 2012.

Edited by:

Masaaki Murakami, Osaka University, Japan

Reviewed by:

Takayuki Yoshimoto, Tokyo Medical University, Japan
Hiroki Yoshida, Saga University Faculty of Medicine, Japan
Daisuke Kamimura, Osaka University, Japan

Copyright: © 2012 Shinohara, Mirakaj and Serhan. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.

*Correspondence: Charles N. Serhan, Center for Experimental Therapeutics, Harvard Institutes of Medicine, 77 Avenue Louis Pasteur, HIM 829, Boston, MA 02115-5727, USA. e-mail: