ArticleAmerican journal of respiratory and critical care medicine2013
Neutrophil elastase degrades cystic fibrosis transmembrane conductance regulator via calpains and disables channel function in vitro and in vivo.
Article in American journal of respiratory and critical care medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers, 1 of them a synthesis that pooled it.
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Who cites it
63 citing papers in PubMed, 1 synthesis or guideline pooled it, 103 citations in OpenAlex.
- Neutrophil elastase in bronchiectasis.Respiratory research · 2017Pooled it
- Ivacaftor for Chronic Obstructive Pulmonary Disease: Results from a Phase 2, Randomized Controlled Trial.American journal of respiratory and critical care medicine · 2025Trial
- Phase I Studies of Acebilustat: Biomarker Response and Safety in Patients with Cystic Fibrosis.Clinical and translational science · 2017Trial
- Assessment of CFTR Dysfunction and Responsiveness to CFTR Modulators in COPD Bronchial Air-Liquid Interface Cultures.International journal of molecular sciences · 2026Article
- Mucoactive Agents in Muco-Obstructive Lung Diseases: A Critical Reappraisal of Pharmacological Effects and Clinical Outcomes.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Treatment of chronic obstructive pulmonary disease: current pipeline and new opportunities.Nature reviews. Drug discovery · 2026Review
- The Challenges of Detecting Neutrophil CFTR.Journal of innate immunity · 2026Review
- People with cystic fibrosis with high sputum neutrophil elastase on elexacaftor-tezacaftor-ivacaftor exhibit worse pulmonary function and pro-inflammatory airway milieu.Scientific reports · 2025Article
- Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation.Cell host & microbe · 2025Article
- Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Quantifying abnormal alveolar microstructure in cystic fibrosis lung disease via hyperpolarizedJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2024Article
- Neutrophil serine proteases in cystic fibrosis: role in disease pathogenesis and rationale as a therapeutic target.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Abnormal functional lymphoid tolerance and enhanced myeloid exocytosis are characteristics of resting and stimulated PBMCs in cystic fibrosis patients.Frontiers in immunology · 2024Article
- Article
- Diagnosis and Management of Cystic Fibrosis Exacerbations.Seminars in respiratory and critical care medicine · 2023Review
- Cystic fibrosis transmembrane conductance regulator in COPD: a role in respiratory epithelium and beyond.The European respiratory journal · 2023Review
- Biological and Genetic Mechanisms of COPD, Its Diagnosis, Treatment, and Relationship with Lung Cancer.Biomedicines · 2023Review
- Impact ofInternational journal of molecular sciences · 2022Review
- CFTR heterozygosity in severe asthma with recurrent airway infections: a retrospective review.Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology · 2022Article
3 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
rationaleCystic fibrosis transmembrane conductance regulator (CFTR) protein is a chloride channel regulating fluid homeostasis at epithelial surfaces. Its loss of function induces hypohydration, mucus accumulation, and bacterial infections in CF and potentially other lung chronic diseases.
objectivesTo test whether neutrophil elastase (NE) and neutrophil-mediated inflammation negatively impact CFTR structure and function, in vitro and in vivo.
methodsUsing an adenovirus-CFTR overexpression approach, we showed that NE degrades wild-type (WT)- and ΔF508-CFTR in vitro and WT-CFTR in mice through a new pathway involving the activation of intracellular calpains. MEASUREMENTS AND MAIN
resultsCFTR degradation triggered a loss of function, as measured in vitro by channel patch-clamp and in vivo by nasal potential recording in mice. Importantly, this mechanism was also shown to be operative in a Pseudomonas aeruginosa lung infection murine model, and was NE-dependent, because CFTR integrity was significantly protected in NE(-/-) mice compared with WT mice.
conclusionsThese data provide a new mechanism and show for the first time a link between NE-calpains activation and CFTR loss of function in bacterial lung infections relevant to CF and to other chronic inflammatory lung conditions.
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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.