Neutrophil-derived reactive oxygen species in SSc
Abstract
OBJECTIVE: Reactive oxygen species (ROS) are implicated in the pathogenesis of SSc. Neutrophils constitute a major source of ROS during inflammation. Here, we examined endogenous and stimulated ex vivo ROS production of SSc neutrophils compared with control neutrophils with and without prior priming with TNF-α. METHODS: ROS generation was measured using luminol-enhanced chemiluminescence. Neutrophils isolated from SSc patients and healthy controls were unprimed or were primed with TNF-α. ROS production was stimulated in vitro with phorbol 12-myristate 13-acetate (PMA) and formyl-met-leu-phe (fMLP). To examine the effects of serum mediators on ROS generation, control neutrophils were also stimulated with SSc or control serum. RESULTS: Neutrophil stimulation with PMA and fMLP resulted in a greater increase in ROS generation in SSc neutrophils compared with controls. However, unstimulated SSc neutrophils generated lower levels of ROS than controls. SSc neutrophils demonstrated an increased response to fMLP in the absence of in vitro TNF-α priming indicating priming of SSc neutrophils in vivo. SSc serum did not stimulate neutrophil ROS generation in vitro. CONCLUSION: SSc neutrophils are primed for ROS generation. Neutrophils binding to activated endothelium in SSc, may induce local production of ROS, perpetuating endothelial dysfunction and mediating fibrosis.
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Activated neutrophils release reactive oxygen species (ROS).
“Furthermore, activated neutrophils release reactive oxygen species (ROS) (164).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [164]
Neutrophils of SSc patients release more ROS than neutrophils of healthy controls when challenged with TNFα.
“Of note, neutrophils of SSc patients release more ROS than neutrophils of healthy controls when challenged with TNFα (164).”
From Unraveling SSc Pathophysiology; The Myofibroblast (2018) · cites this paper as [164]
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- Authors
- Barnes, T. C., Anderson, M. E., Edwards, S. W., & Moots, R. J.
- Affiliations
- University of Liverpool (GB)
- Venue
- Rheumatology
- Publisher
- Oxford University Press (OUP)
- Published
- 2012-02-20
- Volume
- 51
- Issue
- 7
- Pages
- 1166-1169
- ISSN
- 1462-0324 (ISSN-L)
- 1462-0332
- OpenAlex
- W2133371523
- Cited by
- 57
- References
- 12
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 8 · 2020: 6 · 2019: 2 · 2018: 7 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 3 · 2013: 3 · 2012: 1
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Lara D. Veeken (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Health Sciences › Medicine › Pathology and Forensic Medicine › Systemic Sclerosis and Related Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- systemic sclerosis, neutrophils, reactive oxygen species, neutrophil priming, TNF-α, phorbol myristate acetate, fMLP, endothelial dysfunction, fibrosis
- MeSH terms
- Adult, Aged, Endothelium, Vascular, Female, Follow-Up Studies, Humans, Male, Middle Aged, Neutrophils, Scleroderma, Systemic, Vasodilation, Reactive Oxygen Species, Oxidative Stress, Luminescence
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