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bioRxiv · 10.1101/2025.11.17.688903

Myeloperoxidase impairs mucociliary transport on human airway epithelium

Boboltz, A.·Rathi, V.·Kumar, S.·Duncan, G. A.
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Abstract

Dampening neutrophil-driven inflammation in the airways remains a challenge in treating cystic fibrosis (CF) lung disease. Myeloperoxidase (MPO) is a neutrophilic enzyme that produces reactive oxygen species and is highly concentrated in CF sputum samples. Greater MPO concentrations have been previously correlated with increased mucus plugging in bronchiectasis, suggesting that the enzyme could impair mucociliary transport. MPO reacts competitively with either thiocyanate (SCN-) or chloride (Cl-) in the airways to catalyze the production of hypothiocyanous acid (HOSCN) or hypochlorous acid (HOCl), respectively. HOCl has proved in prior studies to be extremely cytotoxic, while HOSCN can drastically reduce cytotoxicity. The concentration of SCN- in the airways is largely dependent on transport by the cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is dysfunctional in individuals with CF and causes low SCN- concentrations. CFTR modulator therapies likely raise the concentration of SCN- and enhance the production of HOSCN in the airways. We found that MPO inhibits mucociliary transport in vitro in regardless of SCN- concentrations primarily due to increasing the macromolecular components and effective viscosity of airway surface liquid. The impairment of mucus clearance by MPO was similar to neutrophil elastase (NE), another neutrophilic granular enzyme that damages the host tissues and induces the secretion of mucin proteins by the airway epithelium. Overall, these findings identify MPO as a therapeutic target to resolve deficits in airway clearance function in CF and other related muco-obstructive lung diseases.

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Boboltz, A., Rathi, V., Kumar, S., Duncan, G. A.. 2025-11-18. Myeloperoxidase impairs mucociliary transport on human airway epithelium. https://doi.org/10.1101/2025.11.17.688903

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