ArticlePloS one2012
Neutrophil extracellular traps directly induce epithelial and endothelial cell death: a predominant role of histones.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 774 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Sputum Studies of Anti-Citrullinated Protein Antibodies (ACPA) and Rheumatoid Arthritis (RA) Origins
Multicenter Phase II Trial of NRICM102 Combined With Standard Therapy in Pneumonia
Who cites it
774 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,275 citations in OpenAlex.
- The Underlying Mechanisms and Role of Negative Pressure Wound Therapy in Chronic Diabetic Wound Healing: A Systematic Review and Meta-Analysis.International wound journal · 2026Pooled it
- From immunological mechanisms to targeted therapies: a bibliometric analysis in the domain of research concerning neutrophil extracellular traps and pulmonary diseases (2006-2025).Frontiers in immunology · 2026Pooled it
- Aerosolized Dornase Alfa (DNase I) for the Treatment of Severe Respiratory Failure in COVID-19: A Randomized Controlled Trial.Open forum infectious diseases · 2025Trial
- Fostamatinib for Hospitalized Adults With COVID-19 and Hypoxemia: A Randomized Clinical Trial.JAMA network open · 2024Trial
- Neutrophils in cancer.Nature reviews. Cancer · 2026Review
- Neutrophil extracellular traps in cardiovascular disease: Mechanisms and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- Review
- Neutrophil Extracellular Traps in the Tumor Microenvironment: Mechanisms, Immune Regulation, and Implications for Immune Checkpoint Inhibitor Therapy.International journal of molecular sciences · 2026Review
- Basophil Extracellular Traps in Immunity and Disease.Cancers · 2026Review
- Review
- Neutrophil extracellular traps, endothelial injury and use of abatacept for graft-Haematologica · 2026Article
- Bridging the gap: neuroinflammation and the dawn of precision medicine in amyotrophic lateral sclerosis.Translational neurodegeneration · 2026Review
- Article
- Black and White Mulberry Extracts: Phytochemical Profile andPlants (Basel, Switzerland) · 2026Article
- Serum DNASE1L3 level as a potential exploratory biomarker for Behçet's disease: a preliminary study.Clinical rheumatology · 2026Article
- Epigenetic regulation of neutrophil dysfunction in sepsis: mechanisms, biomarkers, and translational challenges.Journal of translational medicine · 2026Review
- Article
- Review
- NETosis associates with human TB lung tissue destruction and disease pathogenesis.EMBO molecular medicine · 2026Article
- Formyl peptide receptor 1 agonism selectively suppresses mitochondria-driven neutrophil extracellular trap formation while preserving antibacterial immunity.Molecular medicine (Cambridge, Mass.) · 2026Article
714 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutrophils play an important role in innate immunity by defending the host organism against invading microorganisms. Antimicrobial activity of neutrophils is mediated by release of antimicrobial peptides, phagocytosis as well as formation of neutrophil extracellular traps (NET). These structures are composed of DNA, histones and granular proteins such as neutrophil elastase and myeloperoxidase. This study focused on the influence of NET on the host cell functions, particularly on human alveolar epithelial cells as the major cells responsible for gas exchange in the lung. Upon direct interaction with epithelial and endothelial cells, NET induced cytotoxic effects in a dose-dependent manner, and digestion of DNA in NET did not change NET-mediated cytotoxicity. Pre-incubation of NET with antibodies against histones, with polysialic acid or with myeloperoxidase inhibitor but not with elastase inhibitor reduced NET-mediated cytotoxicity, suggesting that histones and myeloperoxidase are responsible for NET-mediated cytotoxicity. Although activated protein C (APC) did decrease the histone-induced cytotoxicity in a purified system, it did not change NET-induced cytotoxicity, indicating that histone-dependent cytotoxicity of NET is protected against APC degradation. Moreover, in LPS-induced acute lung injury mouse model, NET formation was documented in the lung tissue as well as in the bronchoalveolar lavage fluid. These data reveal the important role of protein components in NET, particularly histones, which may lead to host cell cytotoxicity and may be involved in lung tissue destruction.
Indexed as
Identifiers
What OpenQuestion holds
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.