Cited by 121Fatty Acid Research and HealthPhagocytosis and Immune RegulationInflammatory mediators and NSAID effects

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Macrophage Proresolving Mediators—the When and Where

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Dalli, Jesmond, Serhan, Charles·2016·Microbiology Spectrum

DOI 10.1128/microbiolspec.mchd-0001-2014PMC PMC4922532

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Abstract

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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Authors: Dalli, J., & Serhan, C.
Affiliations: Brigham and Women's Hospital (US)
ORCID: Dalli, Jesmond
Serhan, Charles
Venue: Microbiology Spectrum
Publisher: American Society for Microbiology
Published: 2016-05-06
Volume: 4
Issue: 3
ISSN: 2165-0497 (ISSN-L)
DOI: 10.1128/microbiolspec.mchd-0001-2014
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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

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