ArticleThe American journal of pathology2018
The Role of Extracellular Histones in Influenza Virus Pathogenesis.
Article in The American journal of pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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Who cites it
64 citing papers in PubMed, 113 citations in OpenAlex.
- Pathway mapping of leukocyte transcriptome in influenza patients reveals distinct pathogenic mechanisms associated with progression to severe infection.BMC medical genomics · 2020Trial
- TRIM47 catalyzes MAVS SUMOylation to safeguard chronic viral infections and tissue inflammation.Cell communication and signaling : CCS · 2026Article
- Transient lung eosinophilia during breakthrough influenza infection in vaccinated mice is associated with protective and balanced Type 1/2 immune responses.Journal of virology · 2025Article
- CitH3, a Druggable Biomarker for Human Diseases Associated with Acute NETosis and Chronic Immune Dysfunction.Pharmaceutics · 2025Review
- Drug repurposing of cyclin-dependent kinase inhibitors for neutrophilic acute respiratory distress syndrome and psoriasis.Journal of advanced research · 2025Review
- NETosis: A key player in autoimmunity, COVID-19, and long COVID.Journal of translational autoimmunity · 2025Review
- Mesenchymal stem cells protect the integrity of the alveolar epithelial barrier through extracellular vesicles by inhibiting MAPK-mediated necroptosis.Stem cell research & therapy · 2025Article
- Recent Advances in Pathogenesis and Anticoagulation Treatment of Sepsis-Induced Coagulopathy.Journal of inflammation research · 2025Review
- Comparative analysis of neutrophil dynamics and disease in SARS-CoV-2 Delta and Omicron variants utilizing anFrontiers in immunology · 2025Article
- Viral sepsis: diagnosis, clinical features, pathogenesis, and clinical considerations.Military Medical Research · 2024Review
- Characterization of Neutrophil Functional Responses to SARS-CoV-2 Infection in a Translational Feline Model for COVID-19.International journal of molecular sciences · 2024Article
- Ally, adversary, or arbitrator? The context-dependent role of eosinophils in vaccination for respiratory viruses and subsequent breakthrough infections.Journal of leukocyte biology · 2024Review
- Gut microbiota-derived acetate attenuates lung injury induced by influenza infection via protecting airway tight junctions.Journal of translational medicine · 2024Article
- Review
- Neutrophil-derived Activin-A moderates their pro-NETotic activity and attenuates collateral tissue damage caused by Influenza A virus infection.Frontiers in immunology · 2024Article
- Inhalation of an RNA aptamer that selectively binds extracellular histones protects from acute lung injury.Molecular therapy. Nucleic acids · 2023Article
- Biomarkers of cell damage, neutrophil and macrophage activation associated with in-hospital mortality in geriatric COVID-19 patients.Immunity & ageing : I & A · 2022Article
- Neutrophil-Lymphocyte Ratio Predicting Case Severity in SARS-CoV-2 Infection: A Review.Cureus · 2022Review
- TRIM18 is a critical regulator of viral myocarditis and organ inflammation.Journal of biomedical science · 2022Article
- Neutrophil subsets and their differential roles in viral respiratory diseases.Journal of leukocyte biology · 2022Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza. Mice infected with influenza virus displayed high accumulation of extracellular histones, with widespread pulmonary microvascular thrombosis. Occluded pulmonary blood vessels with vascular thrombi often exhibited endothelial necrosis surrounded by hemorrhagic effusions and pulmonary edema. Histones released during influenza induced cytotoxicity and showed strong binding to platelets within thrombi in infected mouse lungs. Nasal wash samples from influenza-infected patients also showed increased accumulation of extracellular histones, suggesting a possible clinical relevance of elevated histones in pulmonary injury. Although histones inhibited influenza growth in vitro, in vivo treatment with histones did not yield antiviral effects and instead exacerbated lung pathology. Blocking with antihistone antibodies caused a marked decrease in lung pathology in lethal influenza-challenged mice and improved protection when administered in combination with the antiviral agent oseltamivir. These findings support the pathogenic effects of extracellular histones in that pulmonary injury during influenza was exacerbated. Targeting histones provides a novel therapeutic approach to influenza pneumonia.
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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.