Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 764

12.4.1 Mucin

Mucus is composed of mucins , heavily glycosylated proteins that are encoded
by MUC genes. Glycoproteic mucins have a composition that is dominated by
carbohydrates (up to 80% of the molecular weight). Mucins correspond to less than
2% of the wet weight of the mucus. Mucin size and concentration influence gel
formation.
In the respiratory tract and its annexes, mucin gene expression varies according
to the compartment. The middle ear expresses mainly Muc5b and the Eustachian
tube produces equal amounts of Muc5b and Muc5ac, whereas the tracheobronchial
epithelium synthesizes primarily Muc5ac.
Mucins are characterized by a variable number of tandem repeats — mucin
domain — that constitutes the main component of mucus structure [ 1512 ].
Among 13 identified mucin genes, only 4 (MUC2, MUC5AC, MUC5B, and
MUC6) encode the cysteine-rich motifs of mucin C- and N-termini that are required
for oligomerization. Three of these 4 genes (MUC2, MUC5AC, and MUC5B) are
expressed in airway cells. The 2 predominant mucins in airway mucus — Muc5ac
and Muc5b — have different chemical and physical properties (charge density,
buoyancy, etc.). Mucins of airway mucus constitute a mixture of heterogeneous
glycoproteins that are polydisperse (mass 2-40 MDa; size 0.5-10

m).
Among mucins, Muc5ac and Muc5b form homotypic polymers, i.e., Muc5ac
monomers bind only to Muc5ac and Muc5b monomers to Muc5b. These polymers
that form the mucus gel are mainly structured as long single chains rather than
branches. Entangled, bundled, and possibly crosslinked mucins constitute glycosy-
lated proteic fibers (caliber 3-10 nm) that are suspended in a solution of electrolytes
and other molecules.
Mucins can be divided into 2 subsets according to their location relative to the
wetted epithelial surface. Two major forms of mucin comprise monomers that are
primarily, but not exclusively, located at the cell surface and oligomers that are
secreted [ 1556 ].
Secreted, gel-forming mucins are entirely extracellular. The majority of mucins
produced in the lung belong to the gel-forming subset. The most notable members
are Muc5ac and Muc5b ( 90% of the mucin content of sputum) [ 1512 ].

Transmembrane (or membrane-tethered) mucins, such as Muc1, Muc4, and
Muc16 (

∼

10% of the mucin content), have a single membrane-spanning domain,
a short cytoplasmic tail, and an extensive extracellular segment. 17 Other members
of the mucin family (Muc1, Muc4, Muc7, Muc11, and Muc13) also expressed by

∼

side chain. Four monosaccharides constitute side chains: galactose, fucose, N acetylglucosamine,
and N acetylneuraminic acid (or sialic acid). Carbohydrates can have sulfate residues and sialic
acids that confer a negative charge to the molecule.
17 Other tethered mucins (Muc3a, Muc3b, Muc12, Muc13, Muc15, Muc17, and Muc20) are either
largely uncharacterized, or are not elaborated in the lung [ 1512 ]. Mucin-3 is produced in lung
tumors; Muc13 and Muc15 in the respiratory tract.