ArticleEBioMedicine2017
Neutrophil Membrane Cholesterol Content is a Key Factor in Cystic Fibrosis Lung Disease.
Article in EBioMedicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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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
28 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Role of Neutrophils on the Ocular Surface.International journal of molecular sciences · 2021Pooled it
- Altered Degranulation and pH of Neutrophil Phagosomes Impacts Antimicrobial Efficiency in Cystic Fibrosis.Frontiers in immunology · 2020Trial
- Targeting cholesterol-driven immunometabolism in cancer: from molecular circuits to clinical translation.Molecular cancer · 2026Review
- Equine Asthma Is Characterised by Severity-Dependent Correlations Between Blood Neutrophil Cholesterol Content and NET Formation.European journal of immunology · 2025Article
- Sepsis-induced hypocholesterolemia is linked to low cardiomyocyte membrane cholesterol and impaired catecholamine responsiveness.Critical care (London, England) · 2025Observational
- Combustion-derived carbon nanoparticles cause delayed apoptosis in neutrophil-like HL-60 cells in vitro and in primed human neutrophilic granulocytes ex vivo.Particle and fibre toxicology · 2025Article
- The influence of interleukin-27 on metabolic fitness in a murine neonatal model of bacterial sepsis.American journal of physiology. Endocrinology and metabolism · 2025Article
- Neutrophil elastase activates macrophage calpain as a mechanism for phagocytic failure.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Review
- Neutrophil-Derived Proteases in Lung Inflammation: Old Players and New Prospects.International journal of molecular sciences · 2024Review
- Laboratory Tools to Predict CFTR Modulator Therapy Effectiveness and to Monitor Disease Severity in Cystic Fibrosis.Journal of personalized medicine · 2024Review
- Myeloid spatial and transcriptional molecular signature of ischemia-reperfusion injury in human liver transplantation.Hepatology communications · 2024Article
- Neutrophil bactericidal activity and host defenses in cystic fibrosis: a narrative review.Journal of thoracic disease · 2023Review
- Review
- Respiratory Infection and Inflammation in Cystic Fibrosis: A Dynamic Interplay among the Host, Microbes, and Environment for the Ages.International journal of molecular sciences · 2023Review
- The Relationship of Cholesterol Responses to Mitochondrial Dysfunction and Lung Inflammation in Chronic Obstructive Pulmonary Disease.Medicina (Kaunas, Lithuania) · 2023Review
- Impact ofInternational journal of molecular sciences · 2022Review
- Alpha-1 Antitrypsin Deficiency: Does Increased Neutrophil Adhesion Contribute to Lung Damage?American journal of respiratory cell and molecular biology · 2022Article
- The Many Roles of Cholesterol in Sepsis: A Review.American journal of respiratory and critical care medicine · 2022Review
- Rescue from Pseudomonas aeruginosa Airway Infection via Stem Cell Transplantation.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
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Authors and funding
16 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIdentification of mechanisms promoting neutrophil trafficking to the lungs of patients with cystic fibrosis (CF) is a challenge for next generation therapeutics. Cholesterol, a structural component of neutrophil plasma membranes influences cell adhesion, a key step in transmigration. The effect of chronic inflammation on neutrophil membrane cholesterol content in patients with CF (PWCF) remains unclear. To address this we examined neutrophils of PWCF to evaluate the cause and consequence of altered membrane cholesterol and identified the effects of lung transplantation and ion channel potentiator therapy on the cellular mechanisms responsible for perturbed membrane cholesterol and increased cell adhesion. METHODOLOGY: PWCF homozygous for the ΔF508 mutation or heterozygous for the G551D mutation were recruited (n=48). Membrane protein expression was investigated by mass spectrometry. The effect of lung transplantation or ivacaftor therapy was assessed by ELISAs, and calcium fluorometric and μ-calpain assays.
findingsMembranes of CF neutrophils contain less cholesterol, yet increased integrin CD11b expression, and respond to inflammatory induced endoplasmic reticulum (ER) stress by activating μ-calpain. In vivo and in vitro, increased μ-calpain activity resulted in proteolysis of the membrane cholesterol trafficking protein caveolin-1. The critical role of caveolin-1 for adequate membrane cholesterol content was confirmed in caveolin-1 knock-out mice. Lung transplant therapy or treatment of PWCF with ivacaftor, reduced levels of circulating inflammatory mediators and actuated increased caveolin-1 and membrane cholesterol, with concurrent normalized neutrophil adhesion.
interpretationResults demonstrate an auxiliary benefit of lung transplant and potentiator therapy, evident by a reduction in circulating inflammation and controlled neutrophil adhesion.
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