ArticleJCI insight2021
NETosis in the pathogenesis of acute lung injury following cutaneous chemical burns.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
35 citing papers in PubMed, 42 citations in OpenAlex.
- The "Double-Edged Sword" of Neutrophils in Trauma: From Pathophysiological Mechanisms to Precision Immunomodulation Strategies.International journal of molecular sciences · 2026Review
- The landscape of protein post-translational modifications in the pathogenesis of acute respiratory distress syndrome.Journal of thoracic disease · 2026Review
- Epigenetic Mechanisms in Perioperative Medicine: From Neuroinflammation and NETosis to Organ Dysfunction and Precision Therapeutics.Biomedicines · 2026Review
- Study on the pro-inflammatory injury of neutrophil extracellular traps in gouty nephropathy.Frontiers in immunology · 2026Review
- The immune dysregulation of fibrosis: insights into immune-fibrotic crosstalk and potential therapeutic targets.Frontiers in immunology · 2026Review
- Genetic and Molecular Interconnections Between Chronic Obstructive Pulmonary Disease and Osteoporosis: Insights from Single-Cell and Mendelian Randomization Analyses.International journal of chronic obstructive pulmonary disease · 2026Article
- NOX2-Dependent Phagocyte Signaling Mediates Silica-Induced Murine Lung Injury via Macrophage-Neutrophil Interactions.Inflammation · 2025Article
- NETosis and pyroptosis of immune cells in sepsis.Journal of translational internal medicine · 2025Article
- Epigenetic Regulation of Neutrophils in ARDS.Cells · 2025Review
- Peptidylarginine Deiminase 4 Deficiency Suppresses Neutrophil Extracellular Trap Formation and Ameliorates Elastase-Induced Emphysema in Mouse Lung.International journal of molecular sciences · 2025Article
- Guardians Turned Culprits: NETosis and Its Influence on Pulmonary Fibrosis Development.Molecular biotechnology · 2025Review
- Persistent neutrophilic inflammation is associated with delayed toxicity of phenylarsine oxide in lungs.Scientific reports · 2025Article
- Sorafenib-induced macrophage extracellular traps via ARHGDIG/IL4/PADI4 axis confer drug resistance through inhibiting ferroptosis in hepatocellular carcinoma.Biology direct · 2024Article
- Recombinant thrombomodulin and recombinant antithrombin attenuate pulmonary endothelial glycocalyx degradation and neutrophil extracellular trap formation in ventilator-induced lung injury in the context of endotoxemia.Respiratory research · 2024Article
- Article
- Epigenetic regulation of pulmonary inflammation.Seminars in cell & developmental biology · 2024Review
- Reduced Bioactive Microbial Products (Pathogen-Associated Molecular Patterns) Contribute to Dysregulated Immune Responses and Impaired Healing in Infected Wounds in Mice with Diabetes.The Journal of investigative dermatology · 2024Article
- A Narrative Review: The Role of NETs in Acute Respiratory Distress Syndrome/Acute Lung Injury.International journal of molecular sciences · 2024Review
- HSP90, a Common Therapeutic Target for Suppressing Skin Injury Caused by Exposure to Chemically Diverse Classes of Blistering Agents.The Journal of pharmacology and experimental therapeutics · 2024Article
- A Murine Model of Vesicant-Induced Acute Lung Injury.The Journal of pharmacology and experimental therapeutics · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Despite the high morbidity and mortality among patients with extensive cutaneous burns in the intensive care unit due to the development of acute respiratory distress syndrome, effective therapeutics remain to be determined. This is primarily because the mechanisms leading to acute lung injury (ALI) in these patients remain unknown. We test the hypothesis that cutaneous chemical burns promote lung injury due to systemic activation of neutrophils, in particular, toxicity mediated by the deployment of neutrophil extracellular traps (NETs). We also demonstrate the potential benefit of a peptidyl arginine deiminase 4 (PAD4) inhibitor to prevent NETosis and to preserve microvascular endothelial barrier function, thus reducing the severity of ALI in mice. Our data demonstrated that phenylarsine oxide (PAO) treatment of neutrophils caused increased intracellular Ca2+-associated PAD4 activity. A dermal chemical burn by lewisite or PAO resulted in PAD4 activation, NETosis, and ALI. NETs disrupted the barrier function of endothelial cells in human lung microvascular endothelial cell spheroids. Citrullinated histone 3 alone caused ALI in mice. Pharmacologic or genetic abrogation of PAD4 inhibited lung injury following cutaneous chemical burns. Cutaneous burns by lewisite and PAO caused ALI by PAD4-mediated NETosis. PAD4 inhibitors may have potential as countermeasures to suppress detrimental lung injury after chemical burns.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.