| Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. | |
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MedLine Citation:
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PMID: 22253477 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Self-resolving inflammatory exudates and lipid mediator metabolomics recently uncovered a new family of potent anti-inflammatory and proresolving mediators biosynthesized by macrophages (MΦs), denoted maresins. Here we determined that maresin 1 (MaR1) produced by human MΦs from endogenous docosahexaenoic acid (DHA) matched synthetic 7R,14S-dihydroxydocosa-4Z,8E,10E,12Z,16Z,19Z-hexaenoic acid. The MaR1 alcohol groups and Z/E geometry of conjugated double bonds were matched using isomers prepared by total organic synthesis. MaR1's potent defining actions were confirmed with synthetic MaR1, i.e., limiting polymorphonuclear neutrophil (PMN) infiltration in murine peritonitis (ng/mouse range) as well as enhancing human macrophage uptake of apoptotic PMNs. At 1 nM, MaR1 was slightly more potent than resolvin D1 in stimulating human MΦ efferocytosis, an action not shared by leukotriene B(4). MaR1 also accelerated surgical regeneration in planaria, increasing the rate of head reappearance. On injury of planaria, MaR1 was biosynthesized from deuterium-labeled (d(5))-DHA that was blocked with lipoxygenase (LOX) inhibitor. MaR1 dose-dependently inhibited TRPV1 currents in neurons, blocked capsaicin (100 nM)-induced inward currents (IC(50) 0.49±0.02), and reduced both inflammation- and chemotherapy-induced neuropathic pain in mice. These results demonstrate the potent actions of MaR1 in regulating inflammation resolution, tissue regeneration, and pain resolution. These findings suggest that chemical signals are shared in resolution cellular trafficking, a key process in tissue regeneration. Moreover, immunoresolvents of the innate immune response, such as MaR1, offer new opportunities for assessing MΦs and their local DHA metabolome in the return to tissue homeostasis.-Serhan, C. N., Dalli, J., Karamnov, S., Choi, A., Park, C.-K., Xu, Z.-Z., Ji, R.-R., Zhu, M., Petasis, N. A. Macrophage proresolving mediator maresin 1 stimulates tissue regeneration and controls pain. |
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Authors:
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Charles N Serhan; Jesmond Dalli; Sergey Karamnov; Alexander Choi; Chul-Kyu Park; Zhen-Zhong Xu; Ru-Rong Ji; Min Zhu; Nicos A Petasis |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-17 |
Journal Detail:
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Title: The FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: - ISSN: 1530-6860 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2012-1-18 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8804484 Medline TA: FASEB J Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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*Center for Experimental Therapeutics and Reperfusion Injury, Harvard Institutes of Medicine, Boston, Massachusetts, USA; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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