Cited by 695Fatty Acid Research and HealthInflammatory mediators and NSAID effectsSphingolipid Metabolism and Signaling

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Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

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Spite, Matthew, Norling, Lucy V., Summers, Lisa, Yang, Rong, Cooper, Dianne, Petasis, Nicos A., Flower, Roderick J., Perretti, Mauro, Serhan, Charles N.·2009·Nature

DOI 10.1038/nature08541PMC PMC2779525

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Abstract

A growing body of evidence indicates that resolution of acute inflammation is an active process. Resolvins are a new family of lipid mediators enzymatically generated within resolution networks that possess unique and specific functions to orchestrate catabasis, the phase in which disease declines. Resolvin D2 (RvD2) was originally identified in resolving exudates, yet its individual contribution in resolution remained to be elucidated. Here, we establish RvD2's potent stereoselective actions in reducing excessive neutrophil trafficking to inflammatory loci. RvD2 decreased leukocyte-endothelial interactions in vivo by endothelial-dependent nitric oxide production, and by direct modulation of leukocyte adhesion receptor expression. In mice with microbial sepsis initiated by caecal ligation and puncture, RvD2 sharply decreased both local and systemic bacterial burden, excessive cytokine production and neutrophil recruitment, while increasing peritoneal mononuclear cells and macrophage phagocytosis. These multi-level pro-resolving actions of RvD2 translate to increased survival from sepsis induced by caecal ligation and puncture and surgery. Together, these results identify RvD2 as a potent endogenous regulator of excessive inflammatory responses that acts via multiple cellular targets to stimulate resolution and preserve immune vigilance.

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Authors: Spite, M., Norling, L. V., Summers, L., Yang, R., Cooper, D., Petasis, N. A., Flower, R. J., Perretti, M., & Serhan, C. N.
Affiliations: Brigham and Women's Hospital (US)
Queen Mary University of London (GB)
University of Southern California (US)
Corresponding author: Serhan, Charles N.
ORCID: Spite, Matthew
Norling, Lucy V.
Yang, Rong
Cooper, Dianne
Petasis, Nicos A.
Perretti, Mauro
Serhan, Charles N.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-10
Volume: 461
Issue: 7268
Pages: 1287-1291
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08541
PMC: PMC2779525
OpenAlex: W1974226247
Cited by: 695
References: 33
Citations by year: 2026: 21 · 2025: 19 · 2024: 35 · 2023: 34 · 2022: 42 · 2021: 49 · 2020: 61 · 2019: 40 · 2018: 40 · 2017: 44 · 2016: 54 · 2015: 45 · 2014: 39 · 2013: 50 · 2012: 48
FWCI: 38.72
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Queen Mary Research Online (Queen Mary University of London) (submittedVersion)
Funders: Wellcome Trust (086867/Z/08/Z, 085903/Z/08)
Versus Arthritis (18445, 18103)
National Institutes of Health (4r37gm038765-19)
National Heart, Lung, and Blood Institute (HL087526, F32HL087526)
National Institute of General Medical Sciences (GM 38765, R01GM038765, 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 (medical) › Inflammatory mediators and NSAID effects
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords: resolvin D2, inflammation resolution, neutrophil trafficking, leukocyte-endothelium interaction, nitric oxide, leukocyte adhesion molecules, cecal ligation and puncture, bacterial load, macrophage phagocytosis, anti-inflammatory agents, host defense
MeSH terms: Animals, Docosahexaenoic Acids, Escherichia coli, Humans, Inflammation, Leukocytes, Macrophages, Male, Mice, Inbred C57BL, Nitric Oxide, Peritoneal Cavity, Peritonitis, Phagocytosis, Reactive Oxygen Species, Sepsis, Endothelial Cells, Mice

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Resolvin D2 is a potent regulator of leukocytes and controls microbial sepsis

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