ArticleJournal of leukocyte biology2021
Histone H4 directly stimulates neutrophil activation through membrane permeabilization.
Article in Journal of leukocyte biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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Who cites it
26 citing papers in PubMed, 38 citations in OpenAlex.
- Role of post-translational modifications in modulating histone reactivity in the extracellular environment.Biochemical Society transactions · 2026Review
- Mechanisms of cardiomyocyte dysfunction induced by extracellular histones.Cell death discovery · 2026Article
- Interkingdom signaling elicited by bacterial extracellular vesicles in human cystic fibrosis airway epithelium and neutrophils.Frontiers in cellular and infection microbiology · 2026Article
- The dual role of neutrophils in sepsis-associated liver injury.Frontiers in immunology · 2025Review
- Cathepsin C from extracellular histone-induced M1 alveolar macrophages promotes NETosis during lung ischemia-reperfusion injury.Redox biology · 2024Article
- Extracellular histones promote TWIK2-dependent potassium efflux and associated NLRP3 activation in alveolar macrophages during sepsis-induced lung injury.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Pathogenic role and clinical significance of neutrophils and neutrophil extracellular traps in idiopathic inflammatory myopathies.Clinical and experimental medicine · 2024Review
- Advances in lung ischemia/reperfusion injury: unraveling the role of innate immunity.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Heparin in sepsis: current clinical findings and possible mechanisms.Frontiers in immunology · 2024Review
- Emerging therapeutic strategies targeting extracellular histones for critical and inflammatory diseases: an updated narrative review.Frontiers in immunology · 2024Review
- Attenuation of neutrophil adhesion and formation of neutrophil extracellular traps by pooled human immune globulins.Frontiers in pharmacology · 2024Article
- Liquid Liver Biopsy for Disease Diagnosis and Prognosis.Journal of clinical and translational hepatology · 2023Review
- Effect of bacillus subtilis strain Z15 secondary metabolites on immune function in mice.BMC genomics · 2023Article
- Neutrophil extracellular traps in systemic autoimmune and autoinflammatory diseases.Nature reviews. Immunology · 2023Review
- Sputum from patients with primary ciliary dyskinesia contains high numbers of dysfunctional neutrophils and inhibits efferocytosis.Respiratory research · 2022Article
- Distinct Brain Proteomic Signatures in Cerebral Small Vessel Disease Rat Models of Hypertension and Cerebral Amyloid Angiopathy.Journal of neuropathology and experimental neurology · 2022Article
- Endothelial Cells Activated by Extracellular Histones Promote Foxp3International journal of molecular sciences · 2022Article
- Neutrophil Extracellular Traps as an Exacerbating Factor in Bacterial Pneumonia.Infection and immunity · 2022Article
- Histones: The critical players in innate immunity.Frontiers in immunology · 2022Review
- Distinct brain regional proteome changes in the rTg-DI rat model of cerebral amyloid angiopathy.Journal of neurochemistry · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular histones have been implicated as a cause of tissue inflammatory injury in a variety of disorders including sepsis, lung, and liver diseases. However, little is known about their interactions with neutrophils and how this might contribute to injury. Here, it is shown that histone H4 acts as neutrophil activator by inducing hydrogen peroxide production, degranulation, cell adhesion, and IL-8 generation. Histone H4 caused permeabilization of the neutrophil membrane (a phenomenon described in other cell types) leading to accelerated cell death. H4 caused sustained rise in neutrophil intracellular calcium that is necessary for respiratory burst activation and degranulation. Convincing evidence was not found for TLRs or ATP receptors in H4 mediated activation. However, pertussis toxin and wortmannin (inhibitors of G protein and PI3K) inhibited H4-induced hydrogen peroxide production and degranulation. These studies suggest that release of histone H4 in sites of infection or inflammation may potentiate neutrophil activation and promote additional inflammatory responses. These studies may provide a better basis for developing novel therapeutic strategies to block neutrophil extracellular trap (NET) and H4-related pathology in sepsis and various forms of lung injury including that induced by viruses like influenza or SAR-CoV2.
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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.