Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells

OBJECTIVE: Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture. METHODS: The cHNECs were prepared from the nasal tissue resected from patients required surgery for chronic sinusitis (CS) or allergic rhinitis (AR). CBD and CBF were measured using videomicroscopy equipped with a high-speed camera. RESULTS: CCis increased CBD by 30%, but not CBF, and decreased intracellular Cl(-) concentration ([Cl(-) ]i ) in cHNECs. The CCis' actions were mimicked by the Cl(-) -free NO3 (-) solution. In contrast, prior treatment of NPPB (20 muM) or CFTR(inh)-172 (1 muM), which increased [Cl(-) ]i by 20%, decreased CBF by 10% and CBD by 25% and inhibited the CCis' actions. However, prior treatment of T16Ainh-A01 (10 muM) did not inhibit the CCis' actions, although it decreased [Cl(-) ]i by 10% and CBD by 15%. Thus, CCis stimulates Cl(-) channels including cystic fibrosis transmembrane conductance regulator (CFTR). Moreover, CCis enhanced the transport of microbeads driven by the beating cilia in cHNECs. The CCis actions were similar in cHNECs from both types of pateints. CONCLUSION: CCis increased CBD by 30% in cHNECs via an [Cl(-) ]i decrease stimulated by activation of Cl(-) channels, including CFTR. CCis may stimulate nasal mucociliary clearance by increasing CBD in patients contracting CS or AR. LEVEL OF EVIDENCE: NA. Laryngoscope, 130:E289-E297, 2020.