Cited by 2,552Fatty Acid Research and HealthPhagocytosis and Immune RegulationInflammatory mediators and NSAID effects

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Resolution of inflammation: the beginning programs the end

Serhan, Charles N, Savill, John·2005·Nature Immunology

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Abstract

Acute inflammation normally resolves by mechanisms that have remained somewhat elusive. Emerging evidence now suggests that an active, coordinated program of resolution initiates in the first few hours after an inflammatory response begins. After entering tissues, granulocytes promote the switch of arachidonic acid-derived prostaglandins and leukotrienes to lipoxins, which initiate the termination sequence. Neutrophil recruitment thus ceases and programmed death by apoptosis is engaged. These events coincide with the biosynthesis, from omega-3 polyunsaturated fatty acids, of resolvins and protectins, which critically shorten the period of neutrophil infiltration by initiating apoptosis. Consequently, apoptotic neutrophils undergo phagocytosis by macrophages, leading to neutrophil clearance and release of anti-inflammatory and reparative cytokines such as transforming growth factor-beta1. The anti-inflammatory program ends with the departure of macrophages through the lymphatics. Understanding these and further details of the mechanism required for inflammation resolution may underpin the development of drugs that can resolve inflammatory processes in directed and controlled ways.

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Authors: Serhan, C. N., & Savill, J.
Affiliations: Brigham and Women's Hospital (US)
Centre for Inflammation Research (GB)
Corresponding author: Serhan, Charles N
ORCID: Serhan, Charles N
Savill, John
Venue: Nature Immunology
Publisher: Springer Science and Business Media LLC
Published: 2005-11-17
Volume: 6
Issue: 12
Pages: 1191-1197
ISSN: 1529-2908 (ISSN-L)
1529-2916
DOI: 10.1038/ni1276
OpenAlex: W2004536682
Cited by: 2,552
References: 80
Citations by year: 2026: 107 · 2025: 94 · 2024: 105 · 2023: 119 · 2022: 141 · 2021: 153 · 2020: 131 · 2019: 123 · 2018: 117 · 2017: 137 · 2016: 100 · 2015: 128 · 2014: 161 · 2013: 157 · 2012: 139
FWCI: 11.93
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Immunology (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
National Institute of General Medical Sciences (GM 38765)
National Institute of Dental and Craniofacial Research (P50DE016191)
Topics: Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
Keywords: inflammation resolution, acute inflammation, lipoxins, resolvins, protectins, omega-3 polyunsaturated fatty acids, arachidonic acid metabolites, prostaglandins, leukotrienes, neutrophil apoptosis, neutrophil clearance, macrophage phagocytosis, TGF-β1, anti-inflammatory cytokines, anti-inflammatory drug development
MeSH terms: Acute Disease, Animals, Humans, Inflammation

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