Airway surface liquid thickness as a function of lung volume in small airways of the guinea pig

1994 ◽  
Vol 77 (5) ◽  
pp. 2333-2340 ◽  
Author(s):  
D. Yager ◽  
T. Cloutier ◽  
H. Feldman ◽  
J. Bastacky ◽  
J. M. Drazen ◽  
...  
Keyword(s):  
Surface Tension ◽  
Epithelial Cells ◽  
Guinea Pig ◽  
Cross Sections ◽  
Lung Volume ◽  
Longitudinal Direction ◽  
Small Airways ◽  
Airway Surface Liquid ◽  
Residual Capacity ◽  
Surface Liquid

The average thickness and distribution of airway surface liquid (ASL) on the luminal surface of peripheral airways were measured in normal guinea pig lungs frozen at functional residual capacity (FRC) and total lung capacity (TLC). Tissue blocks containing cross sections of airways of internal perimeter 0.188–3.342 mm were cut from frozen lungs and imaged by low-temperature scanning electron microscopy (LTSEM). Measurements made from LTSEM images were found to be independent of freezing rate by comparison of measurements at rapid and slow freezing rates. At both lung volumes, the ASL was not uniformly distributed in either the circumferential or longitudinal direction; there were regions of ASL where its thickness was < 0.1 micron, whereas in other regions ASL collected in pools. Discernible liquid on the surfaces of airways frozen at FRC followed the contours of epithelial cells and collected in pockets formed by neighboring cells, a geometry consistent with a low value of surface tension at the air-liquid interface. At TLC airway liquid collected to cover epithelial cells and to form a liquid meniscus, a geometry consistent with a higher value of surface tension. The average ASL thickness (h) was approximately proportional to the square root of airway internal perimeter, regardless of lung volume. For airways of internal perimeter 250 and 1,800 microns, h was 0.9 and 1.8 microns at FRC and 1.7 and 3.7 microns at TLC, respectively. For a given airway internal perimeter, h was 1.99 times thicker at TLC than at FRC; the difference was statistically significant (P < 0.01; 95% confidence interval 1.29–3.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of Airway Surface Liquid on the Isolated Guinea-pig Trachea

1994 ◽  
Vol 7 (4) ◽  
pp. 265-269 ◽  
Author(s):  
H. Rahmoune ◽  
K.L. Shephard
Keyword(s):  
Guinea Pig ◽  
Airway Surface Liquid ◽  
Surface Liquid

Erythromycin increases bactericidal activity of surface liquid in human airway epithelial cells

2005 ◽  
Vol 289 (4) ◽  
pp. L565-L573 ◽  
Author(s):  
Kota Ishizawa ◽  
Tomoko Suzuki ◽  
Mutsuo Yamaya ◽  
Yu Xia Jia ◽  
Seiichi Kobayashi ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Bactericidal Activity ◽  
Culture Medium ◽  
Airway Epithelial Cells ◽  
Airway Surface Liquid ◽  
Airway Epithelial ◽  
Tracheal Epithelial Cells ◽  
Tracheal Epithelial ◽  
Surface Liquid ◽  
Number Of Bacteria

Macrolide antibiotics have clinical benefits in patients with diffuse panbronchiolitis and in patients with cystic fibrosis. Although many mechanisms have been proposed, the precise mechanisms are still uncertain. We examined the effects of erythromycin on bactericidal activity of airway surface liquid secreted by cultured human tracheal epithelial cells. Airway surface liquid was collected by washing the surface of human tracheal epithelial cells with a sodium solution (40 meq/l). Methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa were incubated with airway surface liquid, and the number of surviving bacteria was examined. The number of bacteria in airway surface liquid from the cells cultured in medium alone was significantly lower than that in the sodium solution. Furthermore, the number of bacteria in airway surface liquid from the cells treated with erythromycin was significantly lower than that in airway surface liquid from the cells treated with solvent alone. The production of mRNA and protein of human β-defensin-1 and human β-defensin-2 was significantly increased by erythromycin. Bactericidal activity of airway surface liquid was observed at low concentrations (40 meq/l) of sodium but not at higher concentrations (≥80 meq/l). Airway surface liquid did not contain significant amounts of antibiotics supplemented in the culture medium. Erythromycin at the levels in airway surface liquid and in culture medium did not inhibit bacterial growth. These results suggest that erythromycin may increase bactericidal activity of airway surface liquid in human airway epithelial cells through human β-defensins production and reduce susceptibility of the airway to bacterial infection.

scholarly journals Small Molecule Anion Carriers Correct Abnormal Airway Surface Liquid Properties in Cystic Fibrosis Airway Epithelia

2020 ◽  
Vol 21 (4) ◽  
pp. 1488 ◽  
Author(s):  
Ambra Gianotti ◽  
Valeria Capurro ◽  
Livia Delpiano ◽  
Marcin Mielczarek ◽  
María García-Valverde ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Fluid Composition ◽  
Airway Surface Liquid ◽  
Airway Epithelia ◽  
Drug Candidates ◽  
Cystic Fibrosis Airway ◽  
Functional Models ◽  
Cftr Protein ◽  
Surface Liquid

Cystic fibrosis (CF) is a genetic disease characterized by the lack of cystic fibrosis transmembrane conductance regulator (CFTR) protein expressed in epithelial cells. The resulting defective chloride and bicarbonate secretion and imbalance of the transepithelial homeostasis lead to abnormal airway surface liquid (ASL) composition and properties. The reduced ASL volume impairs ciliary beating with the consequent accumulation of sticky mucus. This situation prevents the normal mucociliary clearance, favouring the survival and proliferation of bacteria and contributing to the genesis of CF lung disease. Here, we have explored the potential of small molecules capable of facilitating the transmembrane transport of chloride and bicarbonate in order to replace the defective transport activity elicited by CFTR in CF airway epithelia. Primary human bronchial epithelial cells obtained from CF and non-CF patients were differentiated into a mucociliated epithelia in order to assess the effects of our compounds on some key properties of ASL. The treatment of these functional models with non-toxic doses of the synthetic anionophores improved the periciliary fluid composition, reducing the fluid re-absorption, correcting the ASL pH and reducing the viscosity of the mucus, thus representing promising drug candidates for CF therapy.

scholarly journals Esomeprazole Increases Airway Surface Liquid pH in Primary Cystic Fibrosis Epithelial Cells

2018 ◽  
Vol 9 ◽  
Author(s):  
Livia Delpiano ◽  
Joseph J. Thomas ◽  
Annabel R. Yates ◽  
Sarah J. Rice ◽  
Michael A. Gray ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Epithelial Cells ◽  
Airway Surface Liquid ◽  
Surface Liquid

scholarly journals Airway Surface Liquid Osmolality Measured Using Fluorophore-Encapsulated Liposomes

2001 ◽  
Vol 117 (5) ◽  
pp. 423-430 ◽  
Author(s):  
Sujatha Jayaraman ◽  
Yuanlin Song ◽  
A.S. Verkman
Keyword(s):  
Epithelial Cells ◽  
Water Loss ◽  
Airway Epithelial Cells ◽  
Evaporative Water Loss ◽  
Airway Surface Liquid ◽  
Airway Epithelial ◽  
Evaporative Water ◽  
Dry Air ◽  
Surface Liquid ◽  
Sulforhodamine 101

The airway surface liquid (ASL) is the thin layer of fluid coating the luminal surface of airway epithelial cells at an air interface. Its composition and osmolality are thought to be important in normal airway physiology and in airway diseases such as asthma and cystic fibrosis. The determinants of ASL osmolality include epithelial cell solute and water transport properties, evaporative water loss, and the composition of secreted fluids. We developed a noninvasive approach to measure ASL osmolality using osmotically sensitive 400-nm-diam liposomes composed of phosphatidylcholine/cholesterol/polyethylene glycol-phosphatidylcholine (1:0.3:0.08 molar ratio). Calcein was encapsulated in the liposomes at self-quenching concentrations (30 mM) as a volume-sensitive marker, together with sulforhodamine 101 (2 mM) as a volume-insensitive reference. Liposome calcein/sulforhodamine 101 fluorescence ratios responded rapidly (&lt;0.2 s) and stably to changes in solution osmolality. ASL osmolality was determined from calcein/sulforhodamine 101 fluorescence ratios after addition of microliter quantities of liposome suspensions to the ASL. In bovine airway epithelial cells cultured on porous supports at an air–liquid interface, ASL thickness (by confocal microscopy) was 22 μm and osmolality was 325 ± 12 mOsm. In anesthetized mice in which a transparent window was created in the trachea, ASL thickness was 55 μm and osmolality was 330 ± 36 mOsm. ASL osmolality was not affected by pharmacological inhibition of CFTR in airway cell cultures or by genetic deletion of CFTR in knockout mice. ASL osmolality could be increased substantially to &gt;400 mOsm by exposure of the epithelium to dry air; the data were modeled mathematically using measured rates of osmosis and evaporative water loss. These results establish a ratio imaging method to map osmolality in biological compartments. ASL fluid is approximately isosmolar under normal physiological conditions, but can become hyperosmolar when exposed to dry air, which may induce cough and airway reactivity in some patients.

scholarly journals Culture with apically applied healthy or disease sputum alters the airway surface liquid proteome and ion transport across human bronchial epithelial cells.

2021 ◽  
Author(s):  
Maximillian Woodall ◽  
Boris Reidel ◽  
Mehmet Kesimer ◽  
Robert Tarran ◽  
Deborah L Baines
Keyword(s):  
Epithelial Cells ◽  
Ion Transport ◽  
Short Circuit ◽  
Bronchial Epithelial Cells ◽  
Airway Surface Liquid ◽  
Human Bronchial Epithelial Cells ◽  
Bronchial Epithelial ◽  
Surface Liquid

Airway secretions contain many signalling molecules and peptides/proteins that are not found in airway surface liquid (ASL) generated by normal human bronchial epithelial cells (NHBE) in vitro. These play a key role in innate defence and mediate communication between the epithelium, immune cells and the external environment. We investigated how culture of NHBE with apically applied secretions from healthy or disease (Cystic Fibrosis, CF) lungs affected epithelial function with a view to providing better in vitro models of the in vivo environment. NHBE from 6-8 different donors were cultured at air-liquid interface (ALI), with apically applied sputum from normal healthy donors (NLS) or CF donors (CFS) for 2-4 hours, 48 hours or with sputum reapplied over 48 hours. Proteomic analysis was carried out on the sputa and on NHBE ASL before and after culture with sputa. Transepithelial electrical resistance (TEER), short circuit current (Isc) and changes to ASL height were measured. There were 71 proteins common to both sputa but not ASL. The protease:protease inhibitor balance was increased in CFS compared to NLS and ASL. Culture of NHBE with sputa for 48 hours identified additional factors not present in NLS, CFS or ASL alone. Culture with either NLS or CFS for 48 hours increased CFTR activity, calcium activated chloride channel (CaCC) activity and changed ASL height. These data indicate that culture with healthy or disease sputum changes the proteomic profile of ASL and ion transport properties of NHBE and this may increase physiological relevance when using in vitro airway models.

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