Requirements for NADPH oxidase and myeloperoxidase in neutrophil extracellular trap formation differ depending on the stimulus
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Neutrophil NET formation induced by PMA, bacteria, and ionomycin has different requirements for NADPH oxidase activity and myeloperoxidase. Release of NETs by neutrophils is linked with immune protection and host damage. A variety of stimuli promotes NET formation. However, findings from different laboratories often vary, and it is possible that more than one mechanism of NET formation exists. NET formation induced by PMA has been shown to require NADPH oxidase activity, and there is evidence that the granule enzyme MPO is also involved. However, requirements for NADPH oxidase or MPO with other stimuli are less well established. We investigated the role of oxidants in NET formation by human neutrophils induced with PMA, several bacterial genera, and the calcium ionophore ionomycin. With the use of inhibitors of the NADPH oxidase and MPO, oxidant scavengers, and cells from a MPO-deficient individual, we observed that requirements for oxidant generation depend on the stimulus. NADPH oxidase activity was required with PMA and bacterial stimulation but not with ionomycin. Whereas MPO was required for efficient NET formation with PMA, incubation with bacteria induced NETs independently of MPO activity. Although the specific mechanisms whereby oxidants participate in NET formation remain to be clarified, it is possible that other stimuli that mobilize calcium act like ionomycin via an oxidant-independent mechanism, and it cannot be inferred from results with PMA that MPO is required with more physiological stimuli.
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Both NETotic cell death and NET extrusion in the absence of RCD rely on activity of NADPH oxidases.
“both NETotic cell death and NET extrusion in the absence of RCD appears to rely on the activity of NADPH oxidases [724, 736, 737].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [737]
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- Authors
- Parker, H., Dragunow, M., Hampton, M. B., Kettle, A. J., & Winterbourn, C. C.
- Affiliations
- University of Otago (NZ)
- University of Auckland (NZ)
- Corresponding author
- Winterbourn, Christine C
- Venue
- Journal of Leukocyte Biology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-10-01
- Volume
- 92
- Issue
- 4
- Pages
- 841-849
- ISSN
- 0741-5400 (ISSN-L)
- 1938-3673
- OpenAlex
- W2097560724
- Cited by
- 430
- References
- 50
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 32 · 2023: 29 · 2022: 29 · 2021: 39 · 2020: 26 · 2019: 36 · 2018: 39 · 2017: 32 · 2016: 46 · 2015: 27 · 2014: 24 · 2013: 17 · 2012: 4
- FWCI
- 10.03
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Leukocyte Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Health Research Council of New Zealand
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Microbiology › Antimicrobial Peptides and Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- neutrophil extracellular traps, NADPH oxidase, myeloperoxidase, neutrophils, oxidant production, phorbol myristate acetate, bacterial stimulation, ionomycin, calcium ionophore, neutrophil activation
- MeSH terms
- Calcium, Humans, Hypochlorous Acid, Peroxidase, Neutrophils, Tetradecanoylphorbol Acetate, Ionomycin, Reactive Oxygen Species, NADPH Oxidases
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