Cited by 421Fatty Acid Research and HealthInflammatory mediators and NSAID effectsSphingolipid Metabolism and Signaling

Novel Lipid Mediators and Resolution Mechanisms in Acute Inflammation

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Serhan, Charles N.·2010·The American Journal of Pathology

Abstract

Because inflammation is appreciated as a unifying basis of many widely occurring diseases, the mechanisms involved in its natural resolution are of considerable interest. Using contained, self-limited inflammatory exudates and a systems approach, novel lipid-derived mediators and pathways were uncovered in the resolution of inflammatory exudates. These new families of local mediators control both the duration and magnitude of acute inflammation as well as the return of the site to homeostasis in the process of catabasis. This new genus of specialized proresolving mediators (SPM) includes essential fatty acid-derived lipoxins, resolvins, protectins, and, most recently, maresins. These families were named based on their unique structures and potent stereoselective actions. The temporally initiated biosynthesis of SPM and their direct impact on leukocyte trafficking and macrophage-directed clearance mechanisms provide clear evidence that resolution is an active, programmed response at the tissue level. Moreover, SPM that possess anti-inflammatory (ie, limiting PMN infiltration) and proresolving (enhance macrophage uptake and clearance of apoptotic PMN and microbial particles) actions as well as stimulating mucosal antimicrobial responses demonstrate that anti-inflammation and proresolution are different responses of the host and novel defining properties of these molecules. The mapping of new resolution circuits has opened the possibility for understanding mechanisms that lead from acute to chronic inflammation, or to the resolution thereof, as well as to potential, resolution-based immunopharmacological therapies.

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Crossref · 10.2353/ajpath.2010.100322

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  • EPA and DHA are precursors to bioactive lipid metabolites, including specialized proresolving mediators and cytochrome P450-generated monoepoxides, that could contribute to lower CHD risk.

    “Both EPA and DHA are also precursors to bioactive lipid metabolites, including specialized proresolving mediators36 and cytochrome P450–generated monoepoxides,37 that could contribute to lower CHD risk.”
  • Pro-resolving mediators block inflammatory cell influx, promote egress of inflammatory cells, modulate pro-inflammatory T cell responses, and promote clearance of pathogens and dead cells, limiting tissue damage and enabling repair.

    “By activating cell-surface receptors, pro-resolving mediators block inflammatory cell influx and promote the egress of inflammatory cells, modulate pro-inflammatory T cell responses and promote clearance of both pathogens and dead cells (efferocytosis), with all these functions serving to limit tissue damage and to enable the repair of injured tissue29,30.”

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Research works printed but not linked: 7

  1. Serhan CN, Hong S, Gronert K, Colgan SP, Devchand PR, Mirick G, Moussignac R-L: Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter pro-inflammation signals. J Exp Med 2002, 196:1025-1037
  2. Serhan CN: guest ed.: Special Issue on Lipoxins and Aspirin-Trig- gered Lipoxins. Prostaglandins Leukot Essent Fatty Acids 2005, 73(3-4):139 -321
  3. Cassatella MA: The Neutrophil. Edited by Cassatella MA. Basel, Karger 2003
  4. Bannenberg GL, Chiang N, Ariel A, Arita M, Tjonahen E, Gotlinger KH, 1588 Serhan AJP October 2010, Vol. 177, No.
  5. Jin Y, Arita M, Zhang Q, Saban DR, Chauhan SK, Chiang N, Serhan CN, Dana MR: Novel anti-inflammatory and pro-resolving lipid me- diators block inflammatory angiogenesis. Invest Ophthalmol Vis Sci 2009, 50:4743-4752
  6. Wu S-H, Liao P-Y, Yin P-L, Zhang Y-M, Dong L: Elevated expres- sions of 15-lipoxygenase and lipoxin A 4 in children with acute post- streptococcal glomerulonephritis. Am J Pathol 2009, 174:115-122
  7. Gilroy DW, Colville-Nash PR, Willis D, Chivers J, Paul-Clark MJ, Willoughby DA: Inducible cycloxygenase may have anti-inflamma- tory properties. Nat Med 1999, 5:698 -701 155.

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Authors
Serhan, C. N.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Serhan, Charles N.
Venue
The American Journal of Pathology
Publisher
Elsevier BV
Published
2010-10
Volume
177
Issue
4
Pages
1576-1591
ISSN
0002-9440 (ISSN-L)
OpenAlex
W153263572
Cited by
421
References
166
Citations by year
2026: 6 · 2025: 11 · 2024: 17 · 2023: 18 · 2022: 15 · 2021: 27 · 2020: 27 · 2019: 28 · 2018: 26 · 2017: 31 · 2016: 23 · 2015: 26 · 2014: 55 · 2013: 45 · 2012: 38
FWCI
3.99
Type
journal article
Language
en
Open access
Locations
  • American Journal Of Pathology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institutes of Health (GM038765, DK074448, DE019938)
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 › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
inflammation resolution, specialized pro-resolving mediators, lipoxins, resolvins, protectins, maresins, essential fatty acids, leukocyte migration, macrophage clearance, neutrophil infiltration, chronic inflammation, anti-inflammatory mediators, inflammatory exudate
MeSH terms
Animals, Humans, Inflammation, Lipids, Signal Transduction, Inflammation Mediators

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