ArticlePloS one2013
High levels of S100A8/A9 proteins aggravate ventilator-induced lung injury via TLR4 signaling.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 52 citations in OpenAlex.
- Single-cell RNA sequencing reveals intrinsic and microbiota-associated sex differences in murine lung.Mucosal immunology · 2026Article
- A developmentally informed narrative review of Toll-like receptors in adult and pediatric acute respiratory distress syndrome.Annals of translational medicine · 2026Review
- Efficacy of anakinra in reducing progression to organ dysfunction in patients with pneumonia (INSPIRE): a randomised, double-blind, placebo-controlled, phase IIa trial.The Lancet regional health. Europe · 2026Article
- Ventilator-Induced Lung Injury: Mechanotransduction and Potential Therapeutic Targets.MedComm · 2026Review
- Single-Cell RNA Sequencing Reveals Commensal Microbes Amplify Sex-Specific Immune Programming in the Murine Lung.bioRxiv : the preprint server for biology · 2026Article
- The S100A8/A9-NETosis feedback loop in sepsis: potential mechanisms, immune crosstalk, and therapeutic targeting.Frontiers in immunology · 2026Review
- Extracellular vesicle-bound S100A8/A9 is differentially expressed in septic shock and prompts acute lung injury.Respiratory research · 2025Article
- Lung-Brain Axis-Generated Inflammatory Biomarkers in Traumatic Brain Injury and Acute Respiratory Distress Syndrome: Role of Mechanical Ventilation/Stress.Advances in biomarker sciences and technology · 2025Article
- The Modulation of Septic Shock: A Proteomic Approach.International journal of molecular sciences · 2024Article
- Exploring the lung-gut direction of the gut-lung axis in patients with ARDS.Critical care (London, England) · 2024Review
- Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2024Article
- Computational Deciphering of the Role of S100A8 and S100A9 Proteins and Their Changes in the Structure Assembly Influences Their Interaction with TLR4, RAGE, and CD36.The protein journal · 2024Article
- Salivary IgA and vimentin differentiate in vitro SARS-CoV-2 infection: A study of 290 convalescent COVID-19 patients.Mucosal immunology · 2024Article
- Elevated Level of Circulating but Not Urine S100A8/A9 Identifies Poor COVID-19 Outcomes.ACS infectious diseases · 2023Article
- Oxidative Stress and Inflammation in Acute and Chronic Lung Injuries.Antioxidants (Basel, Switzerland) · 2023Review
- A targetable 'rogue' neutrophil-subset, [CD11b+DEspR+] immunotype, is associated with severity and mortality in acute respiratory distress syndrome (ARDS) and COVID-19-ARDS.Scientific reports · 2022Article
- S100A8/A9 in COVID-19 pathogenesis: Impact on clinical outcomes.Cytokine & growth factor reviews · 2022Review
- Association Between Plasma Exosomes S100A9/C4BPA and Latent Tuberculosis Infection Treatment: Proteomic Analysis Based on a Randomized Controlled Study.Frontiers in microbiology · 2022Article
- "Rogue" neutrophil-subset [DEspR+CD11b+/CD66b+] immunotype is an actionable therapeutic target for neutrophilic inflammation-mediated tissue injury -Frontiers in immunology · 2022Article
- High levels of plasma S100A9 at admission indicate an increased risk of death in severe tuberculosis patients.Journal of clinical tuberculosis and other mycobacterial diseases · 2021Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundBacterial products add to mechanical ventilation in enhancing lung injury. The role of endogenous triggers of innate immunity herein is less well understood. S100A8/A9 proteins are released by phagocytes during inflammation. The present study investigates the role of S100A8/A9 proteins in ventilator-induced lung injury.
methodsPulmonary S100A8/A9 levels were measured in samples obtained from patients with and without lung injury. Furthermore, wild-type and S100A9 knock-out mice, naive and with lipopolysaccharide-induced injured lungs, were randomized to 5 hours of spontaneously breathing or mechanical ventilation with low or high tidal volume (VT). In addition, healthy spontaneously breathing and high VT ventilated mice received S100A8/A9, S100A8 or vehicle intratracheal. Furthermore, the role of Toll-like receptor 4 herein was investigated.
resultsS100A8/A9 protein levels were elevated in patients and mice with lung injury. S100A8/A9 levels synergistically increased upon the lipopolysaccharide/high VT MV double hit. Markers of alveolar barrier dysfunction, cytokine and chemokine levels, and histology scores were attenuated in S100A9 knockout mice undergoing the double-hit. Exogenous S100A8/A9 and S100A8 induced neutrophil influx in spontaneously breathing mice. In ventilated mice, these proteins clearly amplified inflammation: neutrophil influx, cytokine, and chemokine levels were increased compared to ventilated vehicle-treated mice. In contrast, administration of S100A8/A9 to ventilated Toll-like receptor 4 mutant mice did not augment inflammation.
conclusionS100A8/A9 proteins increase during lung injury and contribute to inflammation induced by HVT MV combined with lipopolysaccharide. In the absence of lipopolysaccharide, high levels of extracellular S100A8/A9 still amplify ventilator-induced lung injury via Toll-like receptor 4.
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