ArticlePLoS pathogens2015
Extracellular Histones Induce Chemokine Production in Whole Blood Ex Vivo and Leukocyte Recruitment In Vivo.
Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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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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.
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Who cites it
34 citing papers in PubMed, 59 citations in OpenAlex.
- Extracellular Vesicles Released by Picornavirus-Infected Cells Modify Antiviral Immune Cell Responses.Journal of extracellular vesicles · 2026Article
- Regulation of histones in thromboinflammation.Frontiers in immunology · 2026Review
- Integrated cellular, proteomic and metabolomic profiling of immune-related adverse events in non-small cell lung cancer.Frontiers in immunology · 2026Article
- Neutrophil death-more than meets the eye.Experimental hematology · 2025Review
- Article
- Extracellular mixed histones are neurotoxic and modulate select neuroimmune responses of glial cells.PloS one · 2024Article
- Myopia Control Efficacy and Long-Term Safety of a Novel Orthokeratology Lens (MESOK Study)-A Randomized Controlled Clinical Trial Combining Clinical and Tear Proteomics Data.Journal of clinical medicine · 2023Article
- Update of cellular responses to the efferocytosis of necroptosis and pyroptosis.Cell division · 2023Review
- The role of extracellular histones in COVID-19.Journal of internal medicine · 2023Review
- Histones: The critical players in innate immunity.Frontiers in immunology · 2022Review
- Damage-Associated Molecular Patterns As Double-Edged Swords in Sepsis.Antioxidants & redox signaling · 2021Review
- Histone H4 directly stimulates neutrophil activation through membrane permeabilization.Journal of leukocyte biology · 2021Article
- Circulating Histones in Sepsis: Potential Outcome Predictors and Therapeutic Targets.Frontiers in immunology · 2021Review
- Article
- The Role of Non-Immune Cell-Derived Extracellular Vesicles in Allergy.Frontiers in immunology · 2021Review
- The origin of extracellular DNA in bacterial biofilm infections in vivo.Pathogens and disease · 2020Article
- Histone H4 aggravates inflammatory injury through TLR4 in chlorine gas-induced acute respiratory distress syndrome.Journal of occupational medicine and toxicology (London, England) · 2020Article
- Extracellular histones are clinically associated with primary graft dysfunction in human liver transplantation.RSC advances · 2019Article
- Fibronectin-binding protein B (FnBPB) fromThe Journal of biological chemistry · 2019Article
- Osteopontin protects against lung injury caused by extracellular histones.Mucosal immunology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The innate immune system relies to a great deal on the interaction of pattern recognition receptors with pathogen- or damage-associated molecular pattern molecules. Extracellular histones belong to the latter group and their release has been described to contribute to the induction of systemic inflammatory reactions. However, little is known about their functions in the early immune response to an invading pathogen. Here we show that extracellular histones specifically target monocytes in human blood and this evokes the mobilization of the chemotactic chemokines CXCL9 and CXCL10 from these cells. The chemokine induction involves the toll-like receptor 4/myeloid differentiation factor 2 complex on monocytes, and is under the control of interferon-γ. Consequently, subcutaneous challenge with extracellular histones results in elevated levels of CXCL10 in a murine air pouch model and an influx of leukocytes to the site of injection in a TLR4 dependent manner. When analyzing tissue biopsies from patients with necrotizing fasciitis caused by Streptococcus pyogenes, extracellular histone H4 and CXCL10 are immunostained in necrotic, but not healthy tissue. Collectively, these results show for the first time that extracellular histones have an important function as chemoattractants as their local release triggers the recruitment of immune cells to the site of infection.
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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.