Abstract
BackgroundThe mucociliary clearance system driven by beating cilia protects the airways from inhaled microbes and particles. Large particles are cleared by mucus bundles made in submucosal glands by parallel linear polymers of the MUC5B mucins. However, the structural organization and function of the mucus generated in surface goblet cells are poorly understood.MethodsThe origin and characteristics of different mucus structures were studied on live tissue explants from newborn wild-type (WT), cystic fibrosis transmembrane conductance regulator (CFTR) deficient (CF) piglets and weaned pig airways using video microscopy, Airyscan imaging and electron microscopy. Bronchoscopy was performed in juvenile pigs in vivo.ResultsWe have identified a distinct mucus formation secreted from the surface goblet cells with a diameter less than two micrometer. This type of mucus was named mucus threads. With time mucus threads gathered into larger mucus assemblies, efficiently collecting particles. The previously observed Alcian blue stained mucus bundles were around 10 times thicker than the threads. Together the mucus bundles, mucus assemblies and mucus threads cleared the pig trachea from particles.ConclusionsThese results demonstrate that normal airway mucus is more complex and has a more variable structural organization and function than was previously understood. These observations emphasize the importance of studying young objects to understand the function of a non-compromised lung.
Highlights
The mucociliary clearance system driven by beating cilia protects the airways from inhaled microbes and particles
The Alcian blue positive mucus bundles move intermittently and perpendicular to the liquid flow, suggesting that they move by an attachment/detachment mechanism and are intermittently attached to the surface. We proposed that this attachment was mediated by the Mucin 5 Subtype AC (MUC5AC) mucin extending from the surface goblet cells and coating the bundles [7]
Mucus bundles produced by submucosal glands were transported cephalically All experiments were performed in porcine distal trachea or primary bronchi
Summary
The mucociliary clearance system driven by beating cilia protects the airways from inhaled microbes and particles. The mucociliary system protects the lungs from these inhaled particles and microbes and the coordinated beating of multiple cilia drives the flow of liquid cephalad. Using the cationic dye Alcian blue to stain mucus bundles, we quantified the thickness and velocity of the bundles and demonstrated that they were two to three times thicker than the airway surface liquid (ASL). This conclusion is based on our published values for Alcian blue positive
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