Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 754

12.3.1.2 Submucosal Glands

In healthy humans, submucosal glands (thickness 0.15 mm for airway wall thickness
0.64 mm [mean gland-wall ratio range 0.14-0.36] [ 1536 ]) are estimated to provide
most of the upper airway mucus. About half of the amount of intracellular mucins
is stored in submucosal glands. Submucosal glands secrete about 40 times more
mucus than secretory epithelial cells.
The body of the gland is located between the spiral bands of smooth muscle
and cartilage plates. Tracheobronchial submucosal glands are tubular branching
structures. Each gland contains multiple tubules that merge in a collecting duct.
Submucosal glands are only found in cartilagous-walled airways (upper aiways,
trachea, and large bronchi) between the epithelium and cartilage. They abound
down to about generation 10 (airway lumen caliber 1-2 mm) [ 1537 ]. Density of
submucosal glands decays with increasing distance from the pharynx, whereas that
of brush and intermediate cells rises.
In submucosal glands after transplantion in human patients with diseases other
than cystic fibrosis, the secretion rate per gland upon stimulation by vasoactive in-
testinal peptide 6 in tracheal and bronchial glands was 1.0 0.4 nl/mn,

respectively [ 1538 ]. The volume of secretion depends on the Na + -K + -2Cl −
cotransporter and on HCO 3 ion.
Submucosal glands are lined with 2 cell types, proximal mucous and distal serous
cells. Mucous and serous cells constitute approximately 60 and 40% of the gland
volume, respectively [ 1538 ]. Mucous and serous cells secrete a viscoelastic gel and
a lubricating fluid (water and electrolytes) that bathes epithelial cilia, respectively.
At their distal ends (acini), serous cells secrete proteoglycans and numerous
antimicrobial, anti-inflammatory, and anti-oxidant proteins [ 1538 ]. The serous fluid
actually contains lysozyme, which breaks down cell walls and lactoferrin, which
limits iron availability to bacteria, immunoglobulin-A, in addition to transferrin,
albumin, Muc7, serum leukocyte protease inhibitor, and surfactant protein-A [ 1531 ,
1538 ]. Serous fluid washes proximal mucous cells that secrete mucins. Mucous
cells contain acidic glycoproteins, whereas serous ceils produce mainly neutral
glycoproteins.
Cystic fibrosis transmembrane regulator localizes primarily to serous cells.
Elevation of cytosolic Ca 2 + level is supposed to activate secretion of fluid, ions
(Na + ,Cl − ,andHCO 3 ), mucins, and other proteins from both serous and mucous
cells and increase in cytosolic cAMP level to stimulate serous cells and mucin, but
not fluid secretion, from mucous cells [ 1538 ].

± 0.2 and 1.1 ±

C2A domain. The ubiquitous variant ubMUnc13-2 is similar to MUnc13-1, as it contains a
C2A domain. Isoforms MUnc13-1, MUnc13-2, and MUnc13-3 complex individually with Rab3
and Rab3-interacting protein (RIM) GTPases in a trimer required for exocytosis of neuronal
synaptic vesicles and endocrine secretory granules. Protein Unc13 was identified from gene
mutations in Caenorhabditis elegans that cause a severe uncoordinated phenotype, i.e., paralysis.
6 VIP

neurons localize around submucosal glands, in addition to smooth muscle layer, lamina
propria, and walls of pulmonary and bronchial arteries (Sect. 12.3.1.4 ). Moreover, VIP lodges also
in mastocytes.

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