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Macrophage Proresolving Mediators—the When and Where
Open accessAbstract
Macrophages and neutrophils orchestrate acute inflammation and host defense as well as the resolution phase and return to homeostasis. In this article, we review the contribution of macrophages to local lipid mediator (LM) levels and the regulation of macrophage LM profiles by polymorphonuclear neutrophils and neutrophil-derived microparticles. We carried out LM metabololipidomics, profiling distinct phagocytes: neutrophils (PMNs), apoptotic PMNs, and macrophages. Efferocytosis increased specialized proresolving mediator (SPM) biosynthesis, including resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles. In studies using deuterium-labeled precursors ( d 8 -arachidonic acid, d 5 -eicosapentaenoic acid, and d 5 -docosahexaenoic acid), apoptotic PMNs and microparticles contributed to SPM biosynthesis during efferocytosis. Assessment of macrophage LM profiles in M2 macrophages demonstrated higher SPM levels in this macrophage subset, including maresin 1 (MaR1), and lower amounts of leukotriene B 4 (LTB 4 ) and prostaglandins than in M1. Apoptotic PMN uptake by both macrophage subtypes led to modulation of their LM profiles. LTB 4 was downregulated in M2, whereas SPMs including lipoxin A 4 were increased. Conversely, uptake of apoptotic PMNs by M2 macrophages reduced (∼25%) overall LMs. MaR1 displays potent tissue-regenerative and antinociceptive actions in addition to its proresolving and anti-inflammatory actions. In addition, the MaR1 biosynthetic intermediate 13 S ,14 S -epoxy-maresin is also bioactive, inhibiting LTB 4 biosynthesis and switching macrophage phenotypes from M1 to M2. Together, these results establish LM signature profiles of human phagocytes and related subpopulations. They demonstrate microparticle regulation of macrophage-specific endogenous LMs during defined stages of acute inflammation and their dynamic changes in human primary phagocytes.
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“In addition, SPM biosynthesis is higher in M2-like macrophages than in M1-like macrophages and increases further in response to efferocytosis161.”
From Inflammation and its resolution in atherosclerosis: mediators and therapeutic opportunities (2019) · cites this paper as [161]
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Metadata
- Authors
- Dalli, J., & Serhan, C.
- Affiliations
- Brigham and Women's Hospital (US)
- Venue
- Microbiology Spectrum
- Publisher
- American Society for Microbiology
- Published
- 2016-05-06
- Volume
- 4
- Issue
- 3
- ISSN
- 2165-0497 (ISSN-L)
- PMC
- PMC4922532
- OpenAlex
- W2473681996
- Cited by
- 121
- References
- 89
- Citations by year
- 2026: 9 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 15 · 2021: 16 · 2020: 12 · 2019: 12 · 2018: 14 · 2017: 8
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Microbiology Spectrum (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (P01GM095467, R01GM038765)
- 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
- specialized pro-resolving mediators, macrophages, neutrophils, efferocytosis, apoptotic neutrophils, M2 macrophages, M1 macrophages, resolvin D1, resolvin D2, maresin 1, leukotriene B4, lipoxin A4, lipidomics, arachidonic acid, eicosapentaenoic acid, docosahexaenoic acid
- MeSH terms
- Animals, Humans, Macrophages, Neutrophils, Inflammation Mediators, Lipid Metabolism, Cell-Derived Microparticles
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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