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Review
.2006 Jul;35(1):20-8.
doi: 10.1165/rcmb.2006-0082SF. Epub 2006 Mar 9.

Effective mucus clearance is essential for respiratory health

Affiliations
Review

Effective mucus clearance is essential for respiratory health

Scott H Randell et al. Am J Respir Cell Mol Biol.2006 Jul.
No abstract available

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Figures

<b>Figure 1.</b>
Figure 1.
A depiction of ion transport across the apical plasma membrane of airway epithelial cells. Schema describing extracellular nucleotide/nucleoside biochemical networks, sensors (receptors), and regulatory paths controlling effectors (ion channels). Cl− can egress through CFTR after adenosine stimulation of A2b-R or through CaCC after stimulation of P2Y2-R by ATP. Na+ transport is facilitated by ENaC. CF cells will not be able to mount a Cl− response after adenosine due to the absence of functional CFTR. Finally, adenosine (ADO) and inosine (INO) are removed from the airway surface by concentrative nucleoside transporters (CNTs) (63).
<b>Figure 2.</b>
Figure 2.
Histologic evidence for mucus plugging in bronchioles. In early (A) and late (B) CF and in COPD (C) terminal bronchioles are obstructed with mucoid secretions, as is a larger airway in the βENaC transgenic mouse (D).A,C, andD are reproduced from Refs. , , and , respectively, with permission.
<b>Figure 3.</b>
Figure 3.
Perfluorocarbon-osmium fixed mouse trachea as studied by transmission electron microscopy reveals an organized structure in the extracellular space surrounding the cilia and microvilli. Luminal air is above and the apical cell surface is at the bottom. (Courtesy of Dr. R. Pickles, the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.)
<b>Figure 4.</b>
Figure 4.
The two-layer model of mucus innate defense. The near-cell surface domain around the cilia and microvilli (periciliary layer = PCL) contains cell surface tethered mucins and other molecules such as glycolipids. The overlying mucus layer is functionally organized by secreted, gel-forming mucins (long strands) interacting with globular proteins to produce the viscoelastic properties required for particle retention and transport.
<b>Figure 5.</b>
Figure 5.
The role of water in the structure and function of the “two-layer” mucus clearance system. Under normal conditions (center panel), there is sufficient water to hydrate the periciliary layer and mucus layer and mucus transport proceeds at normal rates (60 μm/s). Addition of water (and salt) to the surface selectively swells the mucus layer, maintaining apposition of the mucus and periciliary layers (left panel). Reduction in viscoelasticity may account for the observed acceleration of mucus transport (∼ 100 μm/s) under highly hydrated conditions. Loss of water (and salt) from the airway surface collapses both the periciliary and mucus layers, producing mucus adhesion to cell surfaces (right panel).
<b>Figure 6.</b>
Figure 6.
Cell culture/physiologic system to measure ASL volume homeostasis and mucus transport in well-differentiated human bronchial epithelial (HBE) cells. (A) Perfluorocarbon/osmium fixed HBE culture demonstrating excellent cellular differentiation and discrete periciliary (PCL) and mucus layers. (B) Living HBE culture with cellular (calcein-green) and ASL compartments (Texas-red dextran) labeled and visualized with x-z confocal microscopy. (C) En face view of culture with fluorescent beads trapped in mucus as viewed with time lapse fluorescence microscopy to measure rotational mucus transport. (D) Measurement of ASL height by confocal microscopy and transepithelial electric potentials (Vt) by microelectrodes to measure ASL volume and ion transport homeostasis.
<b>Figure 7.</b>
Figure 7.
ASL volume (height) regulation by normal HBE cultures under static conditions. (A) ASL height measured by x-z confocal microscopy at t = 0 after addition of 20 μl of PBS. (B) Mean data for ASL volume homeostasis after addition of PBS without (squares) or with (triangles) 8-SPT (10−5 M) at 48 h. Theblue area depicts normal periciliary liquid layer height. (C) Confocal images of ASL at 48 h without (top panel) and with (bottom panel) 8-SPT. The 3-μm level in the 8-SPT group represents the minimum volume on the airway surface, when liquid is trapped within flattened cilia. Adapted from Ref. , with permission.
<b>Figure 8.</b>
Figure 8.
ASL volume is increased in normal HBE cultures subjected to phasic motion. Thedark blue line represents ASL height after addition of 20 μl of PBS to the apical surface and maintained under phasic motion conditions. Thelight blue area depicts the normal height of the periciliary layer under static conditions.
<b>Figure 9.</b>
Figure 9.
Intraluminal mucus is site of airways infection in CF. (A) Low power H&E view depicting multiple bacterial colonies (arrows) within luminal mucopurulent material. (B) Higher power H&E view showing robust neutrophil infiltration (arrowheads) through the epithelium and a bacterial colony within mucus (arrow). (C) Alcian yellow-toluidine blue stain of bacteria within intraluminal macrocolony.
<b>Figure 10.</b>
Figure 10.
Mucus becomes closely apposed to the cell surface in CF. A photomicrograph of a frozen section of a CF airway. This preparation prevents artifactual splitting of the luminal contents from the cell surface.Dark pink andblue mucus granules are visible within the epithelium, cell nuclei areclear areas, and the basement membrane is thelight pink line below. Alcian blue-PAS stain.
<b>Figure 11.</b>
Figure 11.
Comparison of ASL volume homeostasis by normal (Nl) and CF airway epithelial cultures under phasic motion conditions. The phasic motion condition delivers shear stress to the epithelial surface that approximates that generatedin vivo by phasic respiration (∼ 0.5 dynes · cm−2). (A) Confocal (x-z) images of Nl (top panels) and CF (bottom panels) ASL with time. (B) ASL height for normal (open bar) and CF (filled bar) at 48 h. (C) Rotational mucus transport at 48 h under static or phasic motion conditions. (D) Reduction in CF ASL height to below normal level (dashed blue line) after addition of apyrase to remove ATP but not after 8-SPT. Adapted from Ref. , with permission.
<b>Figure 12.</b>
Figure 12.
Mucus clearance in patients with CF under baseline conditions and after inhalation of 7% hypertonic saline (HS). (A) Whole lung mucus clearance over 60 min. (B) Twenty-four-hour clearance without (open bar) or with (shaded bar) HS. Theshaded area with dashed line represents 24 h clearance ± 1 SD in normal individuals (n = 12 per group). * Different from basal (P < 0.05). Adapted from Ref. , with permission.
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References

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