Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 745

down to terminal bronchioles) have mucosal surfaces that exhibit mucus flow toward
the esophagus. Mucus is more or less continuously secreted, shed, and recycled,
discarded, or degraded.
Mucus delivery and motion are investigated in the framework of flow and
transport of gases and inhaled particles in the respiratory tract under several alter-
native modes of ventilation together with aerosol transfer and surfactant dynamics,
especially in the terminal airways, where it yields alveolar stability and increased
lung compliance.

12.1 Double-Layered Airway Surface Fluid

The liquid layer at the luminal surface of the respiratory epithelium has 2 strata:
(1) a deep, more aqueous, glycoprotein-free, lubricating region that bathes cilia
(interciliary space 200 nm) — the epithelial lining fluid — that is also called the

periciliary liquid (thickness

∼

∼ 7 m) and (2) a superficial, viscous domain, the gel

or mucus layer .
Membrane-bound mucins contribute to the physical properties of liquid near the
cell wetted surface. They confer the features of an anchored gel rather than a simple
gel on top of a liquid. Mucin-4 is densely expressed on cilia and yields a brush-like
configuration. Tethered mucins form an endoluminal brush [ 1512 ]. This brush layer
establishes a mesh that prevents mucins of the mucus gel layer as well as deposited
inhaled particles to penetrate into the periciliary space and causes mucus to form a
distinct layer. Moreover, it provides lubrication through bound water.
In the current gel-on-liquid mucus clearance model, a mucus gel is propelled
on top of a periciliary fluid layer over the respiratory epithelium that hence baths
cilia. In the gel-on-brush model, the periciliary layer is occupied by membrane-
spanning mucins and mucopolysaccharides tethered to the airway wall wetted
surface (cilia, microvilli, and epithelial surface; mesh structure 20-40 nm) [ 1513 ].
The relatively high concentration of membrane-tethered mucins in the endoluminal
brush layer produces intermolecular repulsion within this layer, which stabilizes the
periciliary liquid against compression by an osmotically active mucus layer. The
relative osmotic moduli of the mucus (

300 Pa)
layers explain that the mucus layer acts as a reservoir for water in the periciliary
liquid, thereby stabilizing the mucus clearance in healthy airways [ 1513 ]. In airway
diseases, when the airway surface is sufficiently dehydrated (the partial osmotic
modulus of the mucus layer exceeds the minimal modulus of the periciliary
brush), the mucus layer compresses the periciliary brush and cilia, slowing down
and eventually stopping mucus clearance [ 1513 ]. Immobile mucus favors chronic
inflammation and bacterial infections. Increase in the partial osmotic modulus of
the mucus layer results from either a decrease in the amount of water solvent, as in
mucovicidosis, or an increase in content of secreted mucins as in chronic obstructive
pulmonary diseases.

∼ 200 Pa) and periciliary brush ( >