Cutting Edge: Lipoxins Rapidly Stimulate Nonphlogistic Phagocytosis of Apoptotic Neutrophils by Monocyte-Derived Macrophages
Open accessAbstract
Lipoxins (LX) are lipoxygenase-derived eicosanoids generated during inflammation. LX inhibit polymorphonuclear neutrophil (PMN) chemotaxis and adhesion and are putative braking signals for PMN-mediated tissue injury. In this study, we report that LXA4 promotes another important step in the resolution phase of inflammation, namely, phagocytosis of apoptotic PMN by monocyte-derived macrophages (Mφ). LXA4 triggered rapid, concentration-dependent uptake of apoptotic PMN. This bioactivity was shared by stable synthetic LXA4 analogues (picomolar concentrations) but not by other eicosanoids tested. LXA4-triggered phagocytosis did not provoke IL-8 or monocyte chemoattractant protein-1 release. LXA4-induced phagocytosis was attenuated by anti-CD36, αvβ3, and CD18 mAbs. LXA4-triggered PMN uptake was inhibited by pertussis toxin and by 8-bromo-cAMP and was mimicked by Rp-cAMP, a protein kinase A inhibitor. LXA4 attenuated PGE2-stimulated protein kinase A activation in Mφ. These results suggest that LXA4 is an endogenous stimulus for PMN clearance during inflammation and provide a novel rationale for using stable synthetic analogues as anti-inflammatory compounds in vivo.
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- Authors
- Godson, C., Mitchell, S., Harvey, K., Petasis, N. A., Hogg, N., & Brady, H. R.
- Affiliations
- University College Dublin (IE)
- University of Southern California (US)
- Imperial Cancer Research Fund , London ,
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-02
- Volume
- 164
- Issue
- 4
- Pages
- 1663-1667
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1531140346
- Cited by
- 638
- References
- 34
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 15 · 2023: 21 · 2022: 33 · 2021: 27 · 2020: 22 · 2019: 26 · 2018: 20 · 2017: 35 · 2016: 25 · 2015: 30 · 2014: 24 · 2013: 31 · 2012: 35
- FWCI
- 5.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Wellcome Trust
- Enterprise Ireland
- University College Dublin
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- lipoxins, lipoxin A4, apoptotic neutrophils, phagocytosis, monocyte-derived macrophages, inflammation resolution, eicosanoids, CD36, protein kinase A, pertussis toxin, neutrophil clearance
- MeSH terms
- Anti-Inflammatory Agents, Non-Steroidal, Cell Adhesion, Dose-Response Relationship, Immunologic, Humans, Hydroxyeicosatetraenoic Acids, Macrophages, Monocytes, Neutrophils, Phagocytosis, Apoptosis, Cyclic AMP-Dependent Protein Kinases, Molecular Mimicry, Lipoxins
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