ArticleBlood2014
A neutrophil intrinsic impairment affecting Rab27a and degranulation in cystic fibrosis is corrected by CFTR potentiator therapy.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers.
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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
101 citing papers in PubMed, 157 citations in OpenAlex.
- Altered Degranulation and pH of Neutrophil Phagosomes Impacts Antimicrobial Efficiency in Cystic Fibrosis.Frontiers in immunology · 2020Trial
- CFTR modulators exert subset-specific phenotype remodeling on circulating neutrophils in cystic fibrosis.ImmunoHorizons · 2026Article
- Intrinsic neutrophil dysregulation in programmed cell death promotes neutrophilic inflammation in cystic fibrosis.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2026Article
- The Challenges of Detecting Neutrophil CFTR.Journal of innate immunity · 2026Review
- Repurposing ivacaftor to attenuate LPS-induced acute lung injury: evidence from a non-cystic fibrosis model.Frontiers in pharmacology · 2026Article
- Harnessing smart nanomaterials to reprogram neutrophil plasticity in immune modulation.Journal of nanobiotechnology · 2025Review
- Innate Immunity in Cystic Fibrosis: Varied Effects of CFTR Modulator Therapy on Cell-to-Cell Communication.International journal of molecular sciences · 2025Review
- Review
- Increased NFAT and NFκB signalling contribute to the hyperinflammatory phenotype in response to Aspergillus fumigatus in a mouse model of cystic fibrosis.PLoS pathogens · 2025Article
- Inhibiting CFTR through inh-172 in primary neutrophils reveals CFTR-specific functional defects.Scientific reports · 2024Article
- Cystic fibrosis.Nature reviews. Disease primers · 2024Review
- Analysis of CFTR mRNA and Protein in Peripheral Blood Mononuclear Cells via Quantitative Real-Time PCR and Western Blot.International journal of molecular sciences · 2024Article
- Aberrant immune programming in neutrophils in cystic fibrosis.Journal of leukocyte biology · 2024Article
- The vacuolar anti-Frontiers in immunology · 2024Article
- Neutrophil bactericidal activity and host defenses in cystic fibrosis: a narrative review.Journal of thoracic disease · 2023Review
- Review
- A Proteomic Survey of the Cystic Fibrosis Transmembrane Conductance Regulator Surfaceome.International journal of molecular sciences · 2023Review
- Dysfunctions of Neutrophils in the Peripheral Blood of Children with Cystic Fibrosis.Biomedicines · 2023Article
- Genome Editing for Cystic Fibrosis.Cells · 2023Review
- Pharmacologic improvement of CFTR function rapidly decreases sputum pathogen density, but lung infections generally persist.The Journal of clinical investigation · 2023Observational
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Studies have endeavored to reconcile whether dysfunction of neutrophils in people with cystic fibrosis (CF) is a result of the genetic defect or is secondary due to infection and inflammation. In this study, we illustrate that disrupted function of the CF transmembrane conductance regulator (CFTR), such as that which occurs in patients with ∆F508 and/or G551D mutations, correlates with impaired degranulation of antimicrobial proteins. We demonstrate that CF blood neutrophils release less secondary and tertiary granule components compared with control cells and that activation of the low-molecular-mass GTP-binding protein Rab27a, involved in the regulation of granule trafficking, is defective. The mechanism leading to impaired degranulation involves altered ion homeostasis caused by defective CFTR function with increased cytosolic levels of chloride and sodium, yet decreased magnesium measured in CF neutrophils. Decreased magnesium concentration in vivo and in vitro resulted in significantly decreased levels of GTP-bound Rab27a. Treatment of G551D patients with the ion channel potentiator ivacaftor resulted in normalized neutrophil cytosolic ion levels and activation of Rab27a, thereby leading to increased degranulation and bacterial killing. Our results confirm that intrinsic alterations of circulating neutrophils from patients with CF are corrected by ivacaftor, thus illustrating additional clinical benefits for CFTR modulator therapy.
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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.