ReviewInternational journal of molecular sciences2018
Excessive Extracellular ATP Desensitizes P2Y2 and P2X4 ATP Receptors Provoking Surfactant Impairment Ending in Ventilation-Induced Lung Injury.
Review in International journal of molecular sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
The trial behind it
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
15 citing papers in PubMed, 28 citations in OpenAlex.
- A genome-wide genetic screen reveals the P2Y2-integrin axis as a stabilizer of EGFR mutants in non-small cell lung cancer (NSCLC).Science advances · 2026Article
- Targeting P2X Receptors-Current Progress in Sepsis.International journal of inflammation · 2025Review
- The Role of The Xihuang Pill in Inhibiting Triple-Negative Breast Cancer Through Immunogenic Cell Death.Breast cancer (Dove Medical Press) · 2025Review
- Wheat phytase potentially protects HT-29 cells from inflammatory nucleotides-induced cytotoxicity.Animal bioscience · 2023Article
- A novel definition and treatment of hyperinflammation in COVID-19 based on purinergic signalling.Purinergic signalling · 2022Review
- Mechanical ventilation induces lung and brain injury through ATP production, P2Y1 receptor activation and dopamine release.Bioengineered · 2022Review
- Targeting purinergic receptors to suppress the cytokine storm induced by SARS-CoV-2 infection in pulmonary tissue.International immunopharmacology · 2021Review
- Role of the Purinergic P2Y2 Receptor in Pulmonary Hypertension.International journal of environmental research and public health · 2021Review
- Time controlled adaptive ventilation™ as conservative treatment of destroyed lung: an alternative to lung transplantation.BMC pulmonary medicine · 2021Article
- A new mode of mechanical ventilation: positive + negative synchronized ventilation.Multidisciplinary respiratory medicine · 2021Article
- Resolving the Ionotropic P2X4 Receptor Mystery Points Towards a New Therapeutic Target for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- P2 Purinergic Signaling in the Distal Lung in Health and Disease.International journal of molecular sciences · 2020Review
- Lung Purinoceptor Activation Triggers Ventilator-Induced Brain Injury.Critical care medicine · 2019Article
- Recruitment Maneuvers and Higher PEEP, the So-Called Open Lung Concept, in Patients with ARDS.Critical care (London, England) · 2019Review
- Purinergic Signaling in Pulmonary Inflammation.Frontiers in immunology · 2019Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stretching the alveolar epithelial type I (AT I) cells controls the intercellular signaling for the exocytosis of surfactant by the AT II cells through the extracellular release of adenosine triphosphate (ATP) (purinergic signaling). Extracellular ATP is cleared by extracellular ATPases, maintaining its homeostasis and enabling the lung to adapt the exocytosis of surfactant to the demand. Vigorous deformation of the AT I cells by high mechanical power ventilation causes a massive release of extracellular ATP beyond the clearance capacity of the extracellular ATPases. When extracellular ATP reaches levels >100 μM, the ATP receptors of the AT II cells become desensitized and surfactant impairment is initiated. The resulting alteration in viscoelastic properties and in alveolar opening and collapse time-constants leads to alveolar collapse and the redistribution of inspired air from the alveoli to the alveolar ducts, which become pathologically dilated. The collapsed alveoli connected to these dilated alveolar ducts are subject to a massive strain, exacerbating the ATP release. After reaching concentrations >300 μM extracellular ATP acts as a danger-associated molecular pattern, causing capillary leakage, alveolar space edema, and further deactivation of surfactant by serum proteins. Decreasing the tidal volume to 6 mL/kg or less at this stage cannot prevent further lung injury.
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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.