Myeloperoxidase impairs mucociliary transport on human airway epithelium.

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 airways. Greater MPO concentrations have previously been correlated with increased mucus plugging in bronchiectasis, suggesting that MPO could impair mucociliary transport. As such, we evaluated the impact of MPO treatment on barrier integrity, mucin production, mucus viscoelasticity and mucociliary transport in fully differentiated human airway epithelial cultures at ionic conditions reflective of healthy and CF-affected airways. Using live-cell imaging and particle velocimetry, we found that MPO inhibits mucociliary transport in vitro at CF-like and normal airway conditions. The impairment of mucus clearance by MPO was similar to that by neutrophil elastase, another neutrophilic granular enzyme that damages the host tissues and impairs airway clearance. We also found that subsequent treatment with the reducing agent, N-acetyl cysteine, could alleviate MPO-mediated mucociliary dysfunction through disulfide bond cleavage. These findings identify MPO as a therapeutic target to resolve deficits in airway clearance function in CF and related muco-obstructive lung diseases.