Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance

Round 1

Reviewer 1 Report

The article “Airway epithelial nucleotide release contributes to mucociliary clearance” is a combination of a short review and an original article, where the original data comprise a set of experiments measuring muociliary clearance, surface liquid height and ciliary beat frequency in tracheal cells from wildtype and Pannexin 1 kockout mice. Although this contribution of original new data is quantitatively quite small, the importance and impact of these findings are nevertheless quite significant, as they demonstrate a contribution of pannexin to mucociliary clearance in a model that contains all cell types (ciliated and goblet cells). In addition, the review article nicely summarizes the plethora of findings about nucleotide release and function in the different cell types, which helps to understand this complex issue better.

Reviewer 2 Report

Authors report on vesicular and conducted pathways that contribute to ATP release from airway epithelial cells, focusing on the vesicular nucleotide transporter, the ATP transporter mediating ATP storage in mucin granules and secretory vesicles and on the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. They showed also that ablation of pannexin 1 reduce airway surface liquid volume production, ciliary  beating, and mucociliary clearance rates.

The manuscript is an excellent review on the purinergic regulation of mucus hydration and clearance.

A brief paragraph dedicated to the described pathways as possible drug targets would be welcome, but I understand that it was not the aim of the review.