Airway Protein May Be Key to Body’s Mucociliary Clearance

MUC5AC, an airway protein, plays an important (and overlooked) role in the body’s mucociliary clearance system, according to research published in Science Advances.

Researchers at the University of Maryland’s Respiratory NanoBioengineering Lab say the ratio between MUC5AC and another airway mucin, MUC5B, likely plays a critical role in airway clearance.

MUC5AC and MUC5B form a hydrogel that can be transported by cilia in order to clear pathogens and debris from the airways. According to researchers, the ratio of MUC5B and MUC5AC is tightly regulated to ensure efficient mucociliary clearance. Too much MUC5AC — which occurs in several chronic respiratory diseases — and the lungs suffer mucociliary clearance impairment, enhanced viscoelastic properties, decreased lung function in chronic bronchitis, and mucus plugging in fatal asthma.

So is MUC5AC even necessary? The researchers discovered it is.

They used CRISPR/Cas9-mediated genome editing tools to delete MUC5AC from a tissue model of the human airway. When they did so, they found swirling, irregular flow patterns unconducive to efficient airway clearance, a university news announcement said. But when MUC5AC was added back into the model, the team immediately fixed the issue.

This discovery shows that the ratio between MUC5B and MUC5AC likely plays a critical role in airway clearance, particularly in diseases like asthma, where overproduction of mucus can lead to severe or even fatal health outcomes.

“Prior to this study, this conveyor belt was thought to be primarily directed by the coordinated motion of cilia. However, we found that the mucus gel plays an active role in maintaining the uniformity of transport on the tissue scale to maximize clearance efficiency.”

According to researchers, the most effective treatment pathway may be restoring the appropriate balance between MUC5B and MUC5AC, and this discovery may one day change therapies that treat pulmonary diseases such as asthma, COPD, and cystic fibrosis.

“Our findings suggest that secretion of MUC5B and MUC5AC offer a means for the airway epithelium to dynamically control mucus transport velocity and flow alignment,” researchers wrote. “Preserving baseline levels of MUC5AC could be important in maintaining flow orientation to facilitate effective removal of pathogens.