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Mitochondrial DNA neutrophil extracellular traps are formed after trauma and subsequent surgery
Open accessAbstract
INTRODUCTION: Neutrophil extracellular traps (NETs) have not been demonstrated after trauma and subsequent surgery. Neutrophil extracellular traps are formed from pure mitochondrial DNA (mtDNA) under certain conditions, which is potently proinflammatory. We hypothesized that injury and orthopedic trauma surgery would induce NET production with mtDNA as a structural component. METHODS: Neutrophils were isolated 8 trauma patients requiring orthopedic surgery postinjury and up to 5 days postoperatively. Four healthy volunteers provided positive and negative controls. Total hip replacement patients acted as an uninjured surgical control group. Neutrophil extracellular traps were visualized with DNA (Hoechst 33342TM/Sytox Green/MitoSox/MitoTracker) stains using live cell fluorescence microscopy with downstream quantitative polymerase chain reaction analysis of DNA composition. RESULTS: Neutrophil extracellular traps were present after injury in all 8 trauma patients. They persisted for 5 days postoperatively. Delayed surgery resulted in NET resolution, but they reformed postoperatively. Total hip replacement patients developed NETs postoperatively, which resolved by day 5. Quantitative polymerase chain reaction analysis of NET-DNA composition revealed that NETs formed after injury and surgery were made of mtDNA with no detectable nuclear DNA component. CONCLUSIONS: Neutrophil extracellular traps formed after major trauma and subsequent surgery contain mtDNA and represent a novel marker of heightened innate immune activation. They could be considered when timing surgery after trauma to prevent systemic NET-induced inflammatory complications.
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“Several reports demonstrate that a considerable fraction of the nucleic acids contained in NETs is of mitochondrial, rather than nuclear, origin [724–728].”
From Molecular mechanisms of cell death: recommendations of the nomenclature committee on cell death 2018. (2018) · cites this paper as [725]
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Metadata
- Authors
- McIlroy, D. J., Jarnicki, A. G., Au, G. G., Lott, N., Smith, D. W., Hansbro, P. M., & Balogh, Z. J.
- Affiliations
- University of Newcastle Australia (AU)
- Hunter Medical Research Institute (AU)
- John Hunter Hospital (AU)
- Corresponding author
- Balogh, Zsolt J.
- Venue
- Journal of Critical Care
- Publisher
- Elsevier BV
- Published
- 2014-12
- Volume
- 29
- Issue
- 6
- Pages
- 1133.e1-1133.e5
- ISSN
- 0883-9441 (ISSN-L)
- OpenAlex
- W2100947278
- Cited by
- 187
- References
- 27
- Citations by year
- 2026: 10 · 2025: 18 · 2024: 20 · 2023: 22 · 2022: 23 · 2021: 17 · 2020: 18 · 2019: 16 · 2018: 12 · 2017: 17 · 2016: 9 · 2015: 5
- FWCI
- 4.70
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Critical Care (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Figshare (submittedVersion)
- UTS ePRESS (University of Technology Sydney) (submittedVersion, other-oa)
- NOVA (University of Newcastle Australia) (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Immunology and Microbiology › Immunology › Inflammation biomarkers and pathways
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- neutrophil extracellular traps, mitochondrial DNA, trauma (physical injury), orthopedic surgery, timing of surgery, total hip arthroplasty, innate immune activation, postoperative inflammation, neutrophils
- MeSH terms
- Adult, DNA, Mitochondrial, Humans, Male, Middle Aged, Neutrophils, Wounds and Injuries, Case-Control Studies, Bacteremia, Systemic Inflammatory Response Syndrome, Arthroplasty, Replacement, Hip, Fractures, Bone, Extracellular Traps
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