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Mucus forms an essential barrier that protects the lungs from inhaled particles, pathogens, and toxicants. However, excessive mucus accumulation contributes to the pathogenesis of all the common diseases of the airways. Therefore, understanding airway mucus function and dysfunction is important for pulmonary medicine. The airway mucus barrier is mobile, continually propelled in a proximal direction by ciliary beating. Ciliary dysfunction causes disease both because of the failure to clear xenobiotics from the lungs and by causing mucus accumulation. Mucus and ciliary biology will be considered together in this chapter as they interact to achieve, or fail to achieve, airway clearance.


Below we consider the roles of airway surface liquid, surface epithelial cells, submucosal glands, and mucociliary and cough clearance in healthy individuals.

Airway Surface Liquid (ASL)

Liquid in the airway lumen is distributed between two distinct layers—a mobile mucus layer and a stationary periciliary layer (Fig. 6-1). Secreted polymeric mucins are the principal macromolecular components of the mucus layer, whereas membrane-tethered mucins and non-mucin glycoconjugates are the principal macromolecular components of the periciliary layer.

Figure 6-1

Airway surface liquid layers. A. Mucus is continuously produced in the conducting airways of the lungs, and swept by ciliary action from distal to proximal airways. After passing through the larynx, mucus is swallowed. B. The mobile mucus layer (light blue) glides over a periciliary layer of higher osmotic modulus (dark blue). C. Airway secretory cells synthesize and secrete mucin polymers that interact with water to form the mobile mucus layer. Ciliated cells are covered by a dense glycocalyx containing glycosaminoglycans, membrane-tethered mucins, and other glycoconjugates that give the periciliary layer its high osmotic modulus. D. Mucin polymers are illustrated in the mucus layer with the protein core shown in black, sugar side chains in blue, and sites of end-to-end polymerization as black circles. Membrane-tethered mucins are shown densely coating cilia, while other glycoconjugates are not illustrated. (Reproduced with permission from Dickey BF: Biochemistry. Walking on solid ground, Science. 2012;337(6097):924–925.)

Mucus Layer

Normal mucus has physical characteristics on the border between a viscous fluid and a soft elastic solid. Its physical state can vary with the extent of hydration and other conditions as described below. Mucus is formed by a dilute network of mucin polymers in aqueous solution, with water accounting for ∼98% of the mass, salts ∼0.9%, globular proteins ∼0.6%, and mucins only ∼0.5%. Mucins are exceedingly large glycoproteins (monomeric masses up to 3 × 106 Da) that link up to form long chains and branched networks. MUC5AC and MUC5B are the major secreted mucins in the airways.1–4 They exhibit similar molecular weights and primary structure (Fig. 6-2A) but differ in function (see ...

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