ArticlePloS one2013
Human neutrophil elastase degrades SPLUNC1 and impairs airway epithelial defense against bacteria.
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 39 papers.
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Who cites it
39 citing papers in PubMed, 52 citations in OpenAlex.
- Phase I Studies of Acebilustat: Biomarker Response and Safety in Patients with Cystic Fibrosis.Clinical and translational science · 2017Trial
- Sputum Biomarkers of Inflammation to Track Acute Respiratory Events in School-Age Children with Cystic Fibrosis.International journal of molecular sciences · 2026Observational
- Inhibition of 5-hydroxyindoleacetic acid to reduce neutrophil extracellular trap production improves lung condition in chronic obstructive pulmonary disease mice.Annals of medicine · 2025Article
- A translational view of airway epithelial dysfunction in COPD.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Is the SPLUNC1-Orai1 axis a critical determinant of lung health?Biochemical Society transactions · 2025Review
- Current perspectives and trends of neutrophil extracellular traps in organ fibrosis: a bibliometric and visualization study.Frontiers in immunology · 2025Review
- NLRP3 Inflammasome Activation Modulates Neutrophil Extracellular Trap Formation and Aggravates Airway Inflammation in Bronchiectasis.Research (Washington, D.C.) · 2025Article
- Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies.Physiological reviews · 2024Review
- Protective effect of Shenqi Wenfei Formula against lipopolysaccharide/cigarette smoke-induced COPD in Rat based on gut microbiota and network pharmacology analysis.Frontiers in microbiology · 2024Article
- Remodeling of Paranasal Sinuses Mucosa Functions in Response to Biofilm-Induced Inflammation.Journal of inflammation research · 2024Review
- The Direct Anti-Virulence but Not Bactericidal Activity of Human Neutrophil Elastase againstInternational journal of molecular sciences · 2023Article
- CC16 drives VLA-2-dependent SPLUNC1 expression.Frontiers in immunology · 2023Article
- Role and Therapeutic Targeting Strategies of Neutrophil Extracellular Traps in Inflammation.International journal of nanomedicine · 2023Review
- SPLUNC1 is a negative regulator of the Orai1 CaPhysiological reports · 2022Article
- Neutrophil extracellular traps in chronic lung disease: implications for pathogenesis and therapy.European respiratory review : an official journal of the European Respiratory Society · 2022Review
- SPLUNC1: a novel marker of cystic fibrosis exacerbations.The European respiratory journal · 2021Article
- CFTR Protein: Not Just a Chloride Channel?Cells · 2021Review
- Degradation of bacterial permeability family member A1 (BPIFA1) by house dust mite (HDM) cysteine protease Der p 1 abrogates immune modulator function.International journal of biological macromolecules · 2020Article
- Immunopathological features of air pollution and its impact on inflammatory airway diseases (IAD).The World Allergy Organization journal · 2020Review
- Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens.Frontiers in immunology · 2020Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundAcute exacerbations of chronic obstructive pulmonary disease (AECOPD) are a significant cause of mortality of COPD patients, and pose a huge burden on healthcare. One of the major causes of AECOPD is airway bacterial (e.g. nontypeable Haemophilus influenzae [NTHi]) infection. However, the mechanisms underlying bacterial infections during AECOPD remain poorly understood. As neutrophilic inflammation including increased release of human neutrophil elastase (HNE) is a salient feature of AECOPD, we hypothesized that HNE impairs airway epithelial defense against NTHi by degrading airway epithelial host defense proteins such as short palate, lung, and nasal epithelium clone 1 (SPLUNC1). METHODOLOGY/MAIN
resultsRecombinant human SPLUNC1 protein was incubated with HNE to confirm SPLUNC1 degradation by HNE. To determine if HNE-mediated impairment of host defense against NTHi was SPLUNC1-dependent, SPLUNC1 protein was added to HNE-treated primary normal human airway epithelial cells. The in vivo function of SPLUNC1 in NTHi defense was investigated by infecting SPLUNC1 knockout and wild-type mice intranasally with NTHi. We found that: (1) HNE directly increased NTHi load in human airway epithelial cells; (2) HNE degraded human SPLUNC1 protein; (3) Recombinant SPLUNC1 protein reduced NTHi levels in HNE-treated human airway epithelial cells; (4) NTHi levels in lungs of SPLUNC1 knockout mice were increased compared to wild-type mice; and (5) SPLUNC1 was reduced in lungs of COPD patients.
conclusionsOur findings suggest that SPLUNC1 degradation by neutrophil elastase may increase airway susceptibility to bacterial infections. SPLUNC1 therapy likely attenuates bacterial infections during AECOPD.
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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.