Abstract

Excessive amounts of sticky mucus in asthma are associated with severe symptoms and increased mortality. Removing mucus from the airways could reduce disease burden in patients. Using microscopic optical coherence tomography (mOCT), we investigated mucus transport in living mice and studied how treatment affects transport.

IL-13 was used to induce asthma symptoms in mice. We used high-speed mOCT to image mucus transport through the intact trachea in spontaneously breathing mice. Mucus release from goblet cells was induced by nebulizing the secretagogue ATP-?-S and isotonic saline (IS), hypertonic saline (HS) or the reducing agent tris(2-carboxyethyl)phosphine (TCEP) were applied intranasally to induce mucus transport. Mucus in the lungs was quantified in AB-PAS-stained sections.

In IL-13-treated mice nebulized ATP-?-S resulted in mucus release as judged by histology but no transport. Mucus was mobilized and transported via the trachea by IS or HS treatment. HS application induced more mucus transport compared to IS. HS, unlike IS, was also able to induce mucus secretion from goblet cells. Both, IS and HS treatment induced a non-uniform transport in the form of mucus chunks. Administration of TCEP following IS or HS application removed mucus chunks and reduced the mucus thickness in the trachea. Similarly, after nebulization of ATP-?-S administration of TCEP prior to application of IS or HS completely prevented thickening of the mucus layer in the trachea.

Both, IS and HS induce transport of sticky mucus in mucus chunks and HS also induces mucus secretion. Our data suggest that, in contrast to IS and HS, TCEP liquefies sticky mucus reducing the likelihood of airway obstruction compared to IS and HS.