Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 748

ion transport occurs in airway epithelia. Several hormones, neurotransmitters, and
other agents regulate ion transport through the cell. On the other hand, paracellular
ion transfer relies on dilation and disruption of tight junctions that result from the
contraction of the actomyosin ring of the cortical cytoskeleton. Like the transcellular
ion transport, the paracellular ion transfer can change quickly [ 1516 ]. Histamine
that can be released by mastocytes binds to its H 1 receptor and provokes a Ca 2 +
influx, hence promoting cell contraction, and a rapid and transient increase in the
paracellular Na + conductance, in addition to a smaller elevation in Cl − conductance.
Airway surface liquid hydration is also controlled by extracellular nucleotides,
such as adenosine triphosphate, uridine triphosphate, and UDP, and nucleosides
such as adenosine. These substances bind to cognate receptors. Nucleotides ATP and
UTP target nucleotides (purinergic) P2Y 2 receptors; UDP binds to receptor P2Y 6 ;
adenosine interacts with A 2B receptor to stimulate Cl − export into the airway lumen
(Vol. 3 - Chap. 7. G-Protein-Coupled Receptors). Moreover, activated P2Y 2 inhibits
Na + absorption by airway epithelial cells. Nucleotides receptors thus participate in
the regulation of airway surface liquid volume. In normal conditions, the respiratory
epithelium adjusts Na + and Cl − fluxes so that stretched cilia are almost completely
bathed in the lubricating epithelial lining fluid. In the airway lumen, released ATP
is converted into adenosine that binds to receptor A 2B (Fig. 12.1 ).
Cyclic motion of the airway wall that is associated with successive lung inflation
and deflation regulates homeostasis of airway surface liquid via nucleotides and
nucleosides [ 1514 ]. Aerodynamical stress applied to the airway wall activates P2Y 2
receptors to increase luminal ATP level. Oscillatory motion in vitro that mimics
tidal volume breathing in vivo favors airway surface liquid production, at least
partly, because of ATP-stimulated nucleotide receptor-mediated ENaC inhibition
and CaCC activation.
Airway surface liquid pH influences activity of ion channels, mucus adhesion to
membranes, and attachment of bacteria and viruses to mucus. The glycocalyx pH
is supposed to be influenced by negative charges of sugar moieties and membrane
phospholipid head groups that can attract H + ion. In addition, glycoaminoglycans
and glycoproteins are sialiated and sulfated, thereby accumulating cations on their
surfaces. In healthy airways, airway surface liquid pH is regulated by H + -K +
ATPase and CFTR-mediated HCO3 − flux through Cl − -HCO 3 exchanger.

12.2 Mucociliary Clearance

Mucociliary clearance is a defense mechanism that prevents accumulation of
inhaled contaminants within the respiratory tract. Mucociliary clearance that com-
prises cough results from continuous flow of airway surface liquid over surfaces of
airway lumens. Usually, airway surface liquid is cleared by cilium-mediated mucus
transport. Normal daily volume of respiratory secretion that arrives at the larynx
is estimated to be about 10 ml, as a part of its water content is reabsorbed via ion
transport.