Maresins: novel macrophage mediators with potent antiinflammatory and proresolving actions
By C. Serhan, Rong Yang, Kimberly Martinod, K. Kasuga, Padmini S. Pillai, T. F. Porter, Sungwhan F. Oh, Matthew Spite. Journal of Experimental Medicine, 2009
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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 (MΦs). 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 MΦs 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 MΦ 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 MΦs in tissue homeostasis, inflammation resolution, wound healing, and host defense.
Subfields: Biochemistry, Nutrition and Dietetics, Pharmacology
View Paper: https://www.semanticscholar.org/paper/f0059701f51cd8af730ae4079ce09f239ce77aff
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Citations in the corpus
- Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA (2015, background): “Charles Serhan, whose laboratory has led research in this area (Serhan et al., 2009; Bannenberg and Serhan, 2010; Dalli et al., 2013; Serhan and Chiang, 2013).”
- Advances in Our Understanding of Oxylipins Derived from Dietary PUFAs. (2015, background): “The functions of 14-HDoHE may be mediated via maresins, given that they have been shown to be involved in resolution of inflammation, tissue regeneration, and analgesia (94, 390), or via other DiHDoHEs, which have similar protective effects, such as the wound healing properties of 14,21-DiHDoHE in m”