Airway Surface Liquid and Respiratory Mucus - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 744

of antimicrobial peptides, and kill pathogens [ 1511 ]. 1 In the nearly sterile distal
respiratory tract of healthy lungs, innate immune epithelial function is reduced
due to small constitutive stimulation, when the mucociliary clearance functions
effectively.
Secretory cells include Clara, goblet, and serous cells (Sect. 12.3.1 ). Various
endo- and exogenous factors modify the secretory cell phenotype. Therefore, the
overall term “secretory cell” is more appropriate to designate non-ciliated cells
that liberate materials in lumens of the respiratory tract. Secretory cells release
mucins as well as antimicrobial (defensins, lysozyme, and immunoglobulin-A),
immunomodulatory (secretoglobins and cytokines), and protective (stable, secretory
trefoil proteins and heregulin) molecules, either constitutively and inducibly, that
can be incorporated into mucus [ 1511 ]. In large airways (internal caliber 2mm),

submucosal glands located between airway smooth muscle and cartilage and
connected to the airway lumen by a duct (ciliated in its downstram segment)
contribute to the secretion of mucins and liquid.
Mucus is a viscoelastic fluid (thickness 2-5

>

m) secreted by the respiratory
epithelium. It not only traps inhaled particles (allergens, carcinogens, dust, microor-
ganisms, and inflammatory debris) that come into contact with it to clear them from
airways, but also protects the mucosa of the tracheobronchial tree from dehydration.
Ciliary motions that are associated with mucus propulsion in the human res-
piratory tract were described in the nineteenth century by Purkinje and Valentin
(1834) and Sharpey (1835). The human respiratory tract and its related cavities and
conduits (nose, sinuses, Eustachian tubes, middle ear, pharynx, trachea, and bronchi

1 Neither resident nor recruited leukocytes are required for innate resistance of the pulmonary
epithelium, although resident leukocytes amplify sensing of pathogen-associated molecular
patterns and signal to adjoining epithelial cells and recruited neutrophil enable microbial
clearance [ 1511 ]. Respiratory epithelial cells respond to stimulated Toll-like receptors (class-1
transmembrane innate immune receptors); they then produce pro-inflammatory and antimicro-
bial mediators. They also use cytosolic NOD-like receptors especially against Streptococcus
pneumoniae, Pseudomonas aeruginosa, Moraxella catarrhalis, Chlamydophila pneumoniae, and
Mycobacterium tuberculosis [ 1511 ]. RIG-I-like receptors are other types of cytosolic pattern
recognition receptors involved in sensing of viruses. Additional innate receptors include the
glycosphingolipid lactosylceramide on the apical surface of lung epithelial cells, which detects
fungal -glucans, and class-A scavenger receptors (e.g., ScaRa1 and ScaRa2), which participate

in lung defense. Moreover, epithelial cells sense the release of constituents from injured neigh-
boring cells (ATP in large quantities, adenosine, urate, and alarmins [e.g., HMGB1, S100a8,
S100a9, and cathelicidin]), activated extracellular proteins (e.g., kallikrein-kinin and complement
cascades), degraded extracellular components (hyaluronan), and inflammatory signals secreted
from leukocytes (cytokines and eicosanoids). Airway epithelial cells express receptors for the C3a
and C5a anaphylatoxins [ 1511 ]. In response to infection or injury, epithelial cells produce pro-
inflammatory cytokines and chemokines as well as small cationic bacteriostatic and bactericidal
peptides, such as β -defensins (constitutive β -defensin-1 and inducile ubeta-defensin-2, -3, and -4)
and cathelicidins, and Large antimicrobial proteins, such as lysozyme and lactoferrin, in addition
to surfactant collectins and lipocalin-2 [ 1511 ].

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