Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 763

Goblet cells possess subapical granules similar to Muc5ac granules that undergo
aCa 2 + -regulated exocytosis [ 1554 ]. These secretory granules contain ATP and
UDP glucose. Stimulated nucleotide P2Y 2 receptor increases cytosolic Ca 2 + con-
centration, hence coupled secretion of mucins and nucleotides, the latter creating
a paracrine signal that enables mucin hydration fitting to mucin release.
Concomitant nucleotide release by exocytosis and calcium-regulated mucin
secretion are elevated in goblet cell metaplasia [ 1555 ]. Increased nucleotide lib-
eration from goblet cell and resultant adenosine accumulation yield a compensatory
mechanisms to hydrate mucins by paracrine control of ion and water secretion by
ciliated cells.
Irritants such as cigarette smoke cause a change in mucus glycoprotein type
within goblet cells, from an acid-to-neutral ratio of about 50:50 to 80:20 [ 1531 ]. The
number of goblet cells increases at the expense of ciliated cells. Prolonged exposure
to irritants leads to an increase in size of submucosal glands and, subsequently, a
reduction in airway diameter. Mucus hypersecretion overwhelms the mucociliary
apparatus and mucociliary clearance is attenuated. A significant part of mucus
removal from lungs results from coughing.

12.4 Mucus Composition

Mucus is a heterogeneous fluid aimed at protecting airways against flow stresses
and chemical damages, entrapping and eliminating inhaled particulate matter and
microorganisms. Suitable quality and quantity of airway surface liquid are necessary
for cilium activity. Respiratory mucus is approximately composed of 90 to 98%
water, 2 to 3% proteins, glycoproteins, and proteoglycans, and 2 to 3% lipids,
carbohydrates, and minerals in addition to DNA (0.02%) and other debris of
shed epithelial cells as well as cells such as neutrophils that can influence mucus
rheology. Mucus constituents are interdependent. Active ion transport across the
epithelial wetted surface modulates airway surface liquid hydration.
Mucus forms a barrier over epithelial cells in the conductive airways that is
composed of highly branched, negatively charged glycoproteins intertwined with
other mucosal constituents (water, salts, and other macromolecules, as well as cel-
lular debris and entrapped particles). Entanglements between mucosal constituents
are stabilized by covalent and non-covalent links, such as hydrogen bonding
and electrostatic and hydrophobic interactions. Crosslinking rises when mucus
hydration decays.
Mucus glycoproteins are produced from glycopeptide subunit with a linear
peptide backbone and linear or branched carbohydrate side chains (2-14 oligosac-
charides). 16 Subunits can be linked by disulfide bonds or a link protein.

16 Hydroxy amino acids serine and threonine that are the most abundant amino acids in the
peptide backbone form the

O glycosidic link with N acetylgalactosamine, the initial sugar in the