Effect of epithelium on mucus secretion from feline tracheal submucosal glands

1989 ◽  
Vol 66 (2) ◽  
pp. 764-770 ◽  
Author(s):  
T. Sasaki ◽  
S. Shimura ◽  
H. Sasaki ◽  
T. Takishima
Keyword(s):  
Airway Epithelium ◽  
Inhibitory Action ◽  
Mucus Secretion ◽  
Submucosal Gland ◽  
Leukotriene D4 ◽  
Lipoxygenase Inhibitors ◽  
Beta Adrenergic Agonists ◽  
Submucosal Glands ◽  
Acid Metabolites ◽  
Mucosal Explants

We studied the effect of airway epithelium on mucus secretion by use of an isolated tracheal submucosal gland preparation reported previously (J. Appl. Physiol. 60: 1237–1247, 1986). Mucus glycoconjugate release from submucosal glands of feline trachea was examined using [3H]glucosamine as a mucus precursor. Isolated glands showed significantly higher secretory responses to cholinergic, alpha-, and beta-adrenergic agonists and dibutyryladenosine 3′,5′-cyclic monophosphate (average 400% of control) than the conventional tracheal mucosal explants, which contained epithelium and submucosal tissues in addition to submucosal glands (average 160% of control). The addition of isolated epithelium depressed the secretory response of isolated glands to the same level as that of tracheal explants. However, the supernatant from isolated epithelium failed to inhibit secretory responses to methacholine in isolated glands, suggesting that the epithelium-derived inhibitory factor to secretion may be short-lived. Leukotriene D4 antagonist (FPL 55712), cyclooxygenase and/or lipoxygenase inhibitors (indomethacin or BW 755C) caused no significant change in the inhibitory action of epithelium, suggesting that the inhibition is not due to arachidonic acid metabolites. The newly found secretory inhibitory action of epithelium is of particular interest in the pathogenesis of hypersecretion associated with epithelial damage.

Effect of anion transport inhibition on mucus secretion by airway submucosal glands

1997 ◽  
Vol 272 (2) ◽  
pp. L372-L377 ◽  
Author(s):  
S. K. Inglis ◽  
M. R. Corboz ◽  
A. E. Taylor ◽  
S. T. Ballard
Keyword(s):  
Cystic Fibrosis ◽  
Anion Transport ◽  
Mucus Secretion ◽  
Disulfonic Acid ◽  
Pathological Changes ◽  
Submucosal Gland ◽  
Anion Secretion ◽  
Submucosal Glands ◽  
Gland Duct

To model the airway glandular defect in cystic fibrosis (CF), the effect of anion secretion blockers on submucosal gland mucus secretion was investigated. Porcine distal bronchi were isolated, pretreated with a Cl- secretion blocker (bumetanide) and/or a combination of blockers to inhibit HCO3- secretion (dimethylamiloride, acetazolamide, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid), and then treated with acetylcholine (ACh), a glandular liquid and mucus secretagogue. Bronchi were then fixed, sectioned, and stained for mucins. Each gland duct was ranked for mucin content from zero (no mucin) to five (duct completely occluded with mucin). Untreated bronchi, bronchi treated only with ACh, and ACh-treated bronchi that received either bumetanide or the HCO3- secretion blockers all exhibited low gland duct mucin content (1.18 +/- 0.34, 0.59 +/- 0.07, 0.65 +/- 0.03, and 0.83 +/- 0.11, respectively). However, pretreatment with both Cl- and HCO3- secretion blockers before ACh addition resulted in substantial and significant ductal mucus accumulation (3.57 +/- 0.22). In situ videomicroscopy studies of intact airways confirmed these results. Thus inhibition of the anion (and presumably liquid) secretion response to ACh leads to mucus obstruction of submucosal gland ducts that resembles the early pathological changes observed in CF.

Muscarinic stimulation of submucosal glands in swine trachea

1988 ◽  
Vol 64 (1) ◽  
pp. 200-209 ◽  
Author(s):  
C. M. Yang ◽  
J. M. Farley ◽  
T. M. Dwyer
Keyword(s):  
Acetylcholine Receptors ◽  
Relative Proportion ◽  
Muscarinic Acetylcholine Receptors ◽  
Mucus Secretion ◽  
Submucosal Gland ◽  
Isolated Cells ◽  
Gland Cells ◽  
Submucosal Glands ◽  
Tracheal Explants

The properties of muscarinic acetylcholine receptors (mAChR) on tracheal explants and isolated submucosal gland cells were determined using [3H]quinuclidinyl benzilate ([3H]QNB) and N-[3H]methylscopolamine ([3H]NMS) as ligands. Analysis of competitive displacement of ([3H]NMS binding by pirenzepine demonstrated the presence of M1- (27 +/- 2%) and M2G- (73 +/- 2%) receptors on isolated tracheal submucosal gland cells (TSGC's) in control. Daily administration of diisopropylfluorophosphate (DFP) inhibited cholinesterase activity by greater than 95%. After 7 days of DFP treatment, [3H]QNB binding to intact TSGC's decreased from 14.2 +/- 0.6 to 6.3 +/- 0.8 fmol/10(6) cells; similarly, [3H]NMS binding fell from 8.1 +/- 1.9 to 2.0 +/- 0.8 fmol/10(6) cells. The loss of mAChR's was predominantly of the M2G subtype with the relative proportion dropping to 33%. In addition, 90% of the receptors assumed the high-affinity state for carbachol displacement of [3H]NMS. Mucus secretion was quantitated by measuring the release of 3H-labeled mucus macromolecules from explants of tracheal submucosal glands and isolated cells. Acetylcholine (ACh), 2 X 10(-5) M, stimulated mucus secretion by 2.5 and 2.3 times the basal rate, respectively. Elimination of acetylcholinesterase (AChe) by DFP increased the ACh sensitivity by 18- and 5-fold. Tracheal explants or TSGC's obtained 2 h after an in vivo DFP treatment showed a 6- and 3-fold ACh stimulation. This ACh sensitivity decreased during the continued daily dosing with DFP such that only a 1.3- and 1.1-fold ACh stimulation was apparent after 7 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Progenitor cells of the adult human airway involved in submucosal gland development

Development ◽  
1995 ◽  
Vol 121 (7) ◽  
pp. 2031-2046 ◽  
Author(s):  
J.F. Engelhardt ◽  
H. Schlossberg ◽  
J.R. Yankaskas ◽  
L. Dudus
Keyword(s):  
Cystic Fibrosis ◽  
Progenitor Cells ◽  
Airway Epithelium ◽  
Progenitor Cell ◽  
Xenograft Model ◽  
Submucosal Gland ◽  
Adult Human ◽  
Human Airway ◽  
Submucosal Glands ◽  
Gland Development

A bronchial xenograft model of the human airway was used to identify submucosal gland progenitor cells within the surface airway epithelium. Lineage analysis using recombinant retroviruses has demonstrated considerable diversity in the cellular composition of expanded clones within reconstituted xenograft airway epithelium. These findings provide evidence for the existence of multiple progenitors in the airway with either limited or pluripotent capacity for differentiation. Furthermore, the development of transgene-expressing submucosal glands was associated with a single subset of surface airway epithelial clones. This gland progenitor cell demonstrated two discernible characteristics consistent with the identification of an airway stem cell including: (1) pluripotent capacity for airway differentiation and (2) a two-fold higher proliferative rate than other observed clone types. The number of progenitor cells involved in gland development was also assessed by clonal analysis using alkaline phosphatase and beta-galactosidase transgenes. These studies demonstrated that more than one airway progenitor cell is involved in the initial stages of gland development. A second explanation for the high prevalence of non-clonality in developing glands was suggested from three-dimensional reconstruction of transgene marked glands. These reconstruction experiments demonstrated that 27% of glands contained more than one duct to the surface airway epithelium. This observation suggests a novel mechanism of gland morphogenesis by which independently formed glands interact to join glandular lumens. Such a mechanism of glandular development and morphogenesis may play an important role in normal submucosal gland development and/or the progression of hypersecretory diseases of the adult human airway as seen in cystic fibrosis, chronic bronchitis and asthma. The identification of progenitor cells with the capacity to form submucosal glands has implications on the targets for gene therapy in cystic fibrosis.

Chloride secretion across distal airway epithelium: relationship to submucosal gland distribution

1995 ◽  
Vol 268 (3) ◽  
pp. L526-L531 ◽  
Author(s):  
S. T. Ballard ◽  
J. D. Fountain ◽  
S. K. Inglis ◽  
M. R. Corboz ◽  
A. E. Taylor
Keyword(s):  
Airway Epithelium ◽  
Short Circuit ◽  
Short Circuit Current ◽  
Chloride Secretion ◽  
Submucosal Gland ◽  
Cl Secretion ◽  
Distal Airway ◽  
Submucosal Glands ◽  
Gland Duct ◽  
Barrier Resistance

To evaluate the possible relationship between submucosal glands and transepithelial Cl- secretion, we compared the bioelectric properties of two distal airway regions: bronchioles, which contain few submucosal glands, and small bronchi, which contain numerous glands. Intact distal bronchi were dissected from the lungs of 4-8 wk old pigs and cannulated with micropipettes and perfused. Transepithelial potential difference (PD), short-circuit current (Isc), and barrier resistance (Rm) in distal bronchi, determined by cable analysis, were -3.0 +/- 0.4 mV, 50.7 +/- 5.9 microA/cm2, and 59.6 +/- 5.9 omega.cm2, respectively (means +/- SE). Bumetanide (10 microM), which blocks Cl- secretion through inhibition of Na(+)-K(+)-2Cl- cotransport, reduced Isc in distal bronchi by 30.0 +/- 5.5 microA/cm2 (59.0% of the total Isc). By comparison, a previous study of porcine distal airways [S.T. Ballard and A.E. Taylor, Am. J. Physiol. 267 (Lung Cell. Mol. Physiol. 11): L79-L84, 1994] determined that bumetamide-sensitive Isc in bronchioles was 2.6 +/- 1.4 microA/cm2 (only 9.0% of the total Isc). Submucosal gland duct openings to the luminal surface were identified microscopically and counted in representative fields. In eight bronchioles, 6.8 +/- 4.4 gland duct openings/cm2 of airway surface were observed, whereas seven distal bronchi contained 916.8 +/- 84.0 gland duct openings/cm2, over a 100-fold difference. These data suggest that a direct relationship may exist between the magnitude of active transepithelial Cl- secretion and the presence of submucosal glands in normal distal airways.

scholarly journals The mechanism of PAR-2 mediated mucus secretion in airway submucosal gland

2010 ◽  
Vol 9 ◽  
pp. S18
Author(s):  
H.-J. Lee ◽  
H.-J. Cho ◽  
D.-M. Shin ◽  
N.-S. Joo ◽  
J.-Y. Choi
Keyword(s):  
Mucus Secretion ◽  
Submucosal Gland

CFTR involvement in chloride, bicarbonate, and liquid secretion by airway submucosal glands

1999 ◽  
Vol 277 (4) ◽  
pp. L694-L699 ◽  
Author(s):  
Stephen T. Ballard ◽  
Laura Trout ◽  
Zsuzsa Bebök ◽  
E. J. Sorscher ◽  
Angela Crews
Keyword(s):  
Cystic Fibrosis ◽  
Channel Blocker ◽  
Polyclonal Antibodies ◽  
Surface Epithelium ◽  
Transmembrane Conductance Regulator ◽  
Submucosal Gland ◽  
Transmembrane Conductance ◽  
Active Secretion ◽  
Submucosal Glands ◽  
Cystic Fibrosis Transmembrane

Previous studies demonstrated that ACh-induced liquid secretion by porcine bronchi is driven by active Cl− and H[Formula: see text] secretion. The present study was undertaken to determine whether this process was localized to submucosal glands and mediated by the cystic fibrosis transmembrane conductance regulator (CFTR). When excised, cannulated, and treated with ACh, porcine bronchi secreted 15.6 ± 0.6 μl ⋅ cm−2 ⋅ h−1. Removal of the surface epithelium did not significantly affect the rate of secretion, indicating that the source of the liquid was the submucosal glands. Pretreatment with diphenylamine-2-carboxylate, a relatively nonselective Cl−-channel blocker, significantly reduced liquid secretion by 86%, whereas pretreatment with DIDS, which inhibits a variety of Cl− channels but not CFTR, had no effect. When bronchi were pretreated with glibenclamide or 5-nitro-2-(3-phenylpropylamino)benzoic acid (both inhibitors of CFTR), the rate of ACh-induced liquid secretion was significantly reduced by 39 and 91%, respectively, compared with controls. Agents that blocked liquid secretion also caused disproportionate reductions in H[Formula: see text] secretion. Polyclonal antibodies to the CFTR bound preferentially to submucosal gland ducts and the surface epithelium, suggesting that this channel was localized to these sites. These data suggest that ACh-induced gland liquid secretion by porcine bronchi is driven by active secretion of both Cl− and H[Formula: see text] and is mediated by the CFTR.

Muscarinic receptor subtypes in feline tracheal submucosal gland secretion

1992 ◽  
Vol 262 (2) ◽  
pp. L223-L228 ◽  
Author(s):  
H. Ishihara ◽  
S. Shimura ◽  
M. Satoh ◽  
T. Masuda ◽  
H. Nonaka ◽  
...  
Keyword(s):  
Muscarinic Receptor ◽  
Gland Secretion ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Submucosal Gland ◽  
Muscarinic Receptor Subtypes ◽  
Binding Assays ◽  
Submucosal Glands ◽  
Electrolyte Secretion ◽  
Quinuclidinyl Benzilate

To determine what muscarinic receptor subtype regulates [Ca2+]i mediating airway submucosal gland secretion, we examined the effects of atropine (Atr), pirenzepine (PZ), 11([2-(diethylamino)methyl-1-piperidinyl] acetyl)-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzo-diazepin-6-one (AF-DX116) and 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP) on methacholine (MCh)-evoked [Ca2+]i rise in acinar cells, and compared this with mucus glycoprotein (MGP) and electrolyte secretion evoked by MCh from submucosal glands isolated from feline trachea. [Ca2+]i was measured with the Ca(2+)-sensitive fluorescent dye, fura 2. We determined MGP secretion by measuring TCA-precipitable 3H-labeled glycoconjugates and electrolyte secretion by the change in the rate constant of 22Na-efflux from isolated glands. Half-maximal inhibitory concentrations (IC50) of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked [Ca2+]i rise were 10(-7) M, 6 x 10(-6) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. IC50 of PZ, AF-DX116, 4-DAMP, and Atr against MCh-evoked MGP secretion were 10(-6) M, 2 x 10(-5) M, 8 x 10(-9) M, and 6 x 10(-9) M, respectively. MCh (10(-5) M)-evoked 22Na efflux was significantly inhibited by 10(-7) M 4-DAMP and 10(-7) M Atr (P less than 0.01, each) but not by 10(-7) M PZ. Receptor binding assays with [3H]quinuclidinyl benzilate showed that the Ki values for PZ, AF-D x 116, 4-DAMP and Atr were 2.2 x 10(-8) M, 6.6 x 10(-7) M, 6.2 x 10(-10) M, and 2.9 x 10(-10) M, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Transport of albumin by the rabbit trachea in vitro

1990 ◽  
Vol 68 (2) ◽  
pp. 726-730 ◽  
Author(s):  
A. M. Price ◽  
S. E. Webber ◽  
J. G. Widdicombe
Keyword(s):  
Bovine Serum Albumin ◽  
Sodium Cyanide ◽  
Organ Bath ◽  
Submucosal Gland ◽  
Cell Secretion ◽  
Mucosal Transport ◽  
Submucosal Glands ◽  
Serous Cell ◽  
Fluorescent Dextran

The rabbit whole trachea was mounted in vitro in an organ bath containing Krebs-Henseleit (KH) solution. When the trachea was air filled there was no resting secretion and none was induced by methacholine (0.02 mM). Histology showed that the trachea has very few submucosal glands. When the trachea was filled with KH, with fluorescent bovine serum albumin in the surrounding KH solution, the rate of transport of albumin into the lumen was measured. Methacholine (0.02 mM) and phenylephrine (0.1 mM) more than doubled the output of albumin, and albuterol (0.1 mM) increased it more than fourfold. Cooling the preparation to 4 degrees C decreased the spontaneous output of albumin to less than one-half control and abolished the increase in output due to albuterol. Addition of sodium cyanide (1 mM) to the preparation abolished the increase in albumin transport due to albuterol. Serosal-to-mucosal transport of fluorescent dextran (mol wt 70,000) was less than one-third that of albumin and was not enhanced by methacholine, phenylephrine, or albuterol. Lysozyme output, an index of serous cell secretion, was barely detectable in controls and was not enhanced by any of the drugs. We conclude that the rabbit trachea has no measurable submucosal gland secretion and that it can actively transport albumin into the lumen via the epithelium. The transport rate is enhanced by methacholine, phenylephrine, and especially by albuterol.

Hypoxemia reflexly increases secretion from tracheal submucosal glands in dogs

1982 ◽  
Vol 52 (6) ◽  
pp. 1416-1419 ◽  
Author(s):  
B. Davis ◽  
R. Chinn ◽  
J. Gold ◽  
D. Popovac ◽  
J. G. Widdicombe ◽  
...  
Keyword(s):  
Carotid Body ◽  
Carotid Sinus ◽  
Gland Secretion ◽  
Submucosal Gland ◽  
Vagus Nerves ◽  
Epithelial Surface ◽  
O2 Concentration ◽  
Submucosal Glands ◽  
Lower Trachea ◽  
Anesthetized Dogs

We anesthetized dogs, ventilated their lungs via the lower trachea, and exposed the epithelial surface of the upper trachea and coated it with powdered tantalum. Secretions from submucosal gland ducts formed elevations (hillocks) in the tantalum layer; we counted the number of hillocks that appeared in a 1.2-cm2 field. In 12 dogs, during normoxemia, 12 +/- 2 hillocks/cm2 formed in 90 s; during severe hypoxemia [fractional inspired O2 concentration (FIO2) = 0.05], 40 +/- 4 hillocks/cm2 formed in 90 s. Injections of sodium cyanide (25–75 micrograms) into the arterial supply to the carotid body also stimulated tracheal submucosal gland secretion. Secretory response to hypoxemia was suppressed by 1) section of both carotid sinus body nerves in six dogs and 2) section of both superior laryngeal nerves and vagus nerves in six other dogs. During mild hypoxemia (FIO2 = 0.10 or 0.15) tracheal submucosal gland secretion still increased. We conclude that hypoxemia increases secretion from submucosal glands in canine trachea by a carotid body chemoreflex.

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