ArticleAmerican journal of physiology. Lung cellular and molecular physiology2022
Circulating extracellular histones exacerbate acute lung injury by augmenting pulmonary endothelial dysfunction via TLR4-dependent mechanism.
Article in American journal of physiology. Lung cellular and molecular physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.
- Global research progress of endothelial cells and ALI/ARDS: a bibliometric analysis.Frontiers in physiology · 2024Pooled it
- AKI as a systemic syndrome and its impact on other organ systems.Critical care (London, England) · 2026Review
- Extracellular Vesicles as Drivers of Lung Endothelial Dysfunction in ARDS: Mechanisms and Therapeutic Opportunities.Comprehensive Physiology · 2026Review
- Emerging biomodels to understand the pathophysiology of sepsis and evaluate new therapeutic strategies targeting extracellular histones.Materials today. Bio · 2026Review
- Barrier breakdown: lung-brain crosstalk in systemic inflammation.Journal of neuroinflammation · 2026Review
- Current Insights into Clinical, Molecular, and Therapeutic Approaches to Acute Respiratory Distress Syndrome.Medical sciences (Basel, Switzerland) · 2026Review
- Innate immune circuits in acute lung injury: macrophage plasticity, ILC crosstalk, and tissue repair failure.Frontiers in immunology · 2026Review
- The Role of Histone Modifications in Acute Lung Injury: Molecular Mechanisms and Potential of Traditional Chinese Medicine Treatment.Journal of inflammation research · 2026Review
- Organ Crosstalk During Injury: Mechanisms of Lung-Kidney Interaction in Critical Illness.Comprehensive Physiology · 2025Review
- Association between early prophylactic heparin therapy and mortality in patients with septic shock secondary to respiratory infections: analysis based on MIMIC-IV database.BMC infectious diseases · 2025Article
- Proteomic Analysis of Nasopharyngeal Aspirate Biomarkers for Prematurity-Related Bronchopulmonary Dysplasia.Chest · 2025Article
- Endothelial Trauma Depends on Surface Charge and Extracellular Calcium Levels.bioRxiv : the preprint server for biology · 2025Article
- Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis.Current issues in molecular biology · 2025Review
- Unfractionated heparin attenuated histone-induced pulmonary endothelial glycocalyx injury through Ang/Tie2 pathway.Journal of inflammation (London, England) · 2025Article
- The EZH2 Inhibitor GSK126 Alleviates Thromboinflammation in Deep Vein Thrombosis by Suppressing TLR4 Signaling via H3K27me3 Modulation.Journal of inflammation research · 2025Article
- [Mechanism of Extracellular Histone-Induced Endothelial Dysfunction Leading to Sepsis-Induced Acute Respiratory Distress Syndrome].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2024Article
- Human pulmonary microvascular endothelial cells respond to DAMPs from injured renal tubular cells.Pulmonary circulation · 2024Article
- Exploring the therapeutic role of early heparin administration in ARDS management: a MIMIC-IV database analysis.Journal of intensive care · 2024Article
- Sepsis-Induced Endothelial Dysfunction: Permeability and Regulated Cell Death.Journal of inflammation research · 2024Review
- Extracellular mixed histones are neurotoxic and modulate select neuroimmune responses of glial cells.PloS one · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Extracellular histones released into the circulation following trauma, sepsis, and ARDS may act as potent damage-associated molecular pattern signals leading to multiple organ failure. Endothelial cell (EC) dysfunction caused by extracellular histones has been demonstrated in vitro and in vivo; however, precise mechanistic details of histone-induced EC dysfunction and exacerbation of ongoing inflammation remain poorly understood. This study investigated the role of extracellular histones in exacerbating preexisting endothelial dysfunction and acute lung injury. Histone subunits H3 and H4, but not H1, H2A, or H2B, induced permeability in human pulmonary EC. H3 and H4 at concentrations above 30 µg/mL caused EC inflammation reflected by activation of the NF-κB pathway, transcriptional activation, and release of cytokines and chemokines including IL-6 and IL-8, and increased mRNA and protein expression of EC adhesion molecules VCAM-1 and ICAM-1. Pharmacological inhibitors targeting Toll-like receptor TLR4 but not TLR2/6, blocked histone-induced EC dysfunction. H3 and H4 also strongly augmented EC permeability and inflammation caused by Gram-negative and Gram-positive bacterial particles, endotoxin, and TNFα. Heparin blocked histone-induced augmentation of EC inflammation caused by endotoxin and TNFα. Injection of histone in mouse models of lung injury caused by bacterial wall lipopolysaccharide (LPS) and heat-killed
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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.