Maresins: Novel macrophage mediators with potent antiinflammatory and proresolving actions
Open accessAbstract
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 (MPhis). 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 MPhis 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 MPhi 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 MPhis in tissue homeostasis, inflammation resolution, wound healing, and host defense.
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The differences in effects of EPA and DHA could be due to structural characteristics of the two fatty acids and their ability to produce different metabolite species.
“The differences identified could be due to structural characteristics of the two fatty acids as well as their ability to produce different metabolite species [137,138].”
From Potential Roles of n-3 PUFAs during Skeletal Muscle Growth and Regeneration (2018) · cites this paper as [137]
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- Authors
- Serhan, C. N., Yang, R., Martinod, K., Kasuga, K., Pillai, P. S., Porter, T. F., Oh, S. F., & Spite, M.
- Affiliations
- Brigham and Women's Hospital (US)
- ORCID
- Venue
- Journal of Experimental Medicine
- Publisher
- Rockefeller University Press
- Published
- 2008-12-22
- Volume
- 206
- Issue
- 1
- Pages
- 15-23
- ISSN
- 0022-1007 (ISSN-L)
- 1540-9538
- PMC
- PMC2626672
- OpenAlex
- W2122405246
- Cited by
- 908
- References
- 33
- Citations by year
- 2026: 36 · 2025: 40 · 2024: 54 · 2023: 47 · 2022: 67 · 2021: 56 · 2020: 59 · 2019: 65 · 2018: 55 · 2017: 54 · 2016: 40 · 2015: 52 · 2014: 60 · 2013: 66 · 2012: 48
- FWCI
- 34.35
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Experimental Medicine (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- National Institutes of Health (4r37gm038765-19, DE016191, GM038765)
- National Institute of General Medical Sciences (R37-GM038765)
- National Institute of Dental and Craniofacial Research (P50DE016191)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- maresins, macrophages, inflammation resolution, docosahexaenoic acid, resolvin E1, protectin D1, peritonitis, lipidomics, wound healing
- MeSH terms
- Animals, Anti-Inflammatory Agents, Non-Steroidal, Cell Movement, Docosahexaenoic Acids, Humans, Leukocytes, Mononuclear, Lipoxygenase, Macrophages, Mice, Inbred Strains, Neutrophils, Peritonitis, Phagocytosis, Autacoids, Stereoisomerism, Zymosan, Eicosapentaenoic Acid, Dinoprostone, Molecular Structure, Macrophages, Peritoneal, Inflammation Mediators, Lipid Metabolism, Mice
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