Neutrophil elastase increases ciliary beat frequency ex-vivo: implications for the bronchiectasis airway

Abstract

Rationale: The neutrophil derived protease, Neutrophil elastase (NE), in patient sputum is a biomarker of bronchiectasis severity. The vicious cycle of bronchiectasis pathogenesis suggests NE reduces ciliary beat frequency (CBF), compromising mucociliary clearance. Early studies assessing high concentration porcine elastase or patient sputum on CBF confirmed this hypothesis. The aim of this study was to investigate the effect of physiological NE concentrations on nasal cilia with the hypothesis that NE inhibitors may be a target for improving mucociliary clearance in bronchiectasis. Methods: Nasal brushing was performed on healthy volunteers (free from respiratory infections for at least 5 weeks) and CBF of nasal epithelial cells in suspension was immediately evaluated by high-speed video light microscopy. Media/buffer alone or NE (0.1 U/ml) +/- NE inhibitor (AZD9668, 10 nM) were added and CBF calculated at 37°C. Results: A cohort of 10 volunteers (mean age: 29.2 years; males: 40%; 100% non smokers;) was selected. The mean (SD) of all CBF measurements was 13.83 (3.46) Hz, with a significant increase after NE exposure (11.1%, P Conclusion: NE, at concentrations present in bronchiectasis sputum, increase CBF. The cause of reduced CBF in bronchiectasis airways and the role of NE in mucociliary clearance require review.