Differential effect of epidermal growth factor on serous and mucous cells in porcine airway submucosal gland

Iwase, Nobuhisa; Sasaki, Tsukasa; Oshiro, Takako; Tamada, Tsutomu; Nara, Masayuki; Sasamori, Kan; Hattori, Toshio; Shirato, Kunio; Maruyama, Yoshio

doi:10.1016/s1569-9048(02)00118-0

Cited by 17 publications

(37 citation statements)

References 23 publications

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“…n ϭ 6, †P Ͻ 0.05 to ACh/flagellin/antiTLR5Ab. Indeed, Vaadnrager and colleagues (47) (17,38,39). Additionally, we have reported that maneuvers anticipating a rise in cAMP failed to potentiate and rather decreased ionic currents in tracheal gland cells (45).…”

Section: Nf-b Il-8 and Cftr-dependent CLmentioning

confidence: 66%

“…]i. Moreover, we found that physiologically relevant, basic secretions from swine tracheal submucosal glands could be triggered by ϳ30 nM of ACh (16,17,31,38,39,44,45). The viability of all tested cells was confirmed by the occurrence of ionic responses after the subsequent addition of 30 nM of ACh.…”

Section: Potentiating Effects Of Flagellin On Ach-induced Ionic Currementioning

confidence: 70%

“…The isolated glands were further dispersed enzymatically by incubating them with enzyme solution containing collagenase (200 U/ml) and DL-DTT (0.31 mg/ml) for 30 min at 37°C. After dispersion and a wash with centrifugation at 180 g, the cells were resuspended in a standard extracellular solution until use, as reported previously (16,17,31,38,39,44,45). In a series of experiments investigating the effect of blocking antibodies, anti-TLR 5 polyclonal antibody (10 g/ml) or nonspecific IgG (10 g/ml) was also preincubated with cells for 1 h at 37°C before use.…”

Section: Methodsmentioning

confidence: 99%

“…Membrane currents were monitored at two different holding potentials (Hps), i.e., 0 and Ϫ80 mV, which roughly corresponded to the Cl Ϫ and K ϩ equilibrium potential. The double current monitoring, i.e., alternate recording of the ionic currents corresponding to Hp of 0 and Ϫ80 mV, was accomplished by applying 200-ms voltage pulses of Ϫ80 mV at a frequency of 2 Hz to the pipette voltage of 0 mV (16,17,31,38,39,44,45 (16,17,31,38,39,44,45). The solutions included an extracellular (bath) solution of 120 mM NaCl, 4.7 mM KCl, 1.13 mM MgCl 2, 1.2 mM CaCl2, 10 mM glucose, and 10 mM HEPES and an intracellular (pipette) solution of 120 mM KCl, 1.13 mM MgCl 2, 0.5 mM EGTA, 1 mM Na2ATP, 10 mM glucose, and 10 mM HEPES.…”

Section: Methodsmentioning

confidence: 99%

“…The procedure to estimate the ionic responses was also applied in our previous reports (17,31,44,45). We first measured the area circumscribed with the current trace (I o or Ii) and baseline for 20 s (area under curve20) by using a digital planimeter (PLACOM, KP-92N; Koizumi, Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

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Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Muramatsu

Tamada²,

Nara

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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-Airway serous secretion is essential for the maintenance of mucociliary transport in airway mucosa, which is responsible for the upregulation of mucosal immunity. Although there are many articles concerning the importance of Tolllike receptors (TLRs) in airway immune systems, the direct relationship between TLRs and airway serous secretion has not been well investigated. Here, we focused on whether TLR5 ligand flagellin, which is one of the components of Pseudomonas aeruginosa, is involved in the upregulation of airway serous secretion. Freshly isolated swine tracheal submucosal gland cells were prepared, and the standard patch-clamp technique was applied for measurements of the whole cell ionic responses of these cells. Flagellin showed potentiating effects on these oscillatory currents induced by physiologically relevant low doses of acetylcholine (ACh) in a dose-dependent manner. These potentiating effects were TLR5 dependent but TLR4 independent. Both nitric oxide (NO) synthase inhibitors and cGMPdependent protein kinase (cGK) inhibitors abolished these flagellininduced potentiating effects. Furthermore, TLR5 was abundantly expressed on tracheal submucosal glands. Flagellin/TLR5 signaling further accelerated the intracellular NO synthesis induced by ACh. These findings suggest that TLR5 takes part in the airway mucosal defense systems as a unique endogenous potentiator of airway serous secretions and that NO/cGMP/cGK signaling is involved in this rapid potentiation by TLR5 signaling. Ca 2ϩ -activated Cl Ϫ channel; nitric oxide; cGMP-dependent protein kinase; patch-clamp; Pseudomonas aeruginosa TRACHEAL SUBMUCOSAL GLANDS secrete mucin, various enzyme proteins, and electrolytes (therefore, water), which serve as a nonspecific airway defense mechanism. Additionally, submucosal glands secrete immunoglobulins to neutralize many microbes, serving as a specific airway defense mechanism (34). Among these airway mucosal defense systems, airway serous secretion plays important roles in hydrating airway surfaces and flushing mucin glycoproteins out of the ducts, contributing to the maintenance of mucociliary transport (2,4,10,24,48). Human, feline, and swine tracheal gland acinar cells generate ionic currents in response to relatively low doses of cholinergic and ␣-adrenergic stimuli, and these currents are activated by the intracellular Ca 2ϩ concentration ([Ca 2ϩ ] i ) raised by these neurotransmitters (16,31,38,44,45). The Ca 2ϩ -activated Cl Ϫ channel (CaCC) may play an important role in physiological basal secretions in the airways. It has recently become known that CaCC composes a newly identified transmembrane protein with unknown function, 16, Ano 1 (TMEM16A), which exists in both the airway surface epithelium and submucosal glands (28,33). Concerning the electrophysiological characteristics of CaCC, we have reported that tyrosine kinase, cyclic-ADP ribose, and nitric oxide (NO)/cGMP/cGMP-dependent protein kinase (cGK) are involved in the intracellular pathway of oscillatory ionic currents evoked by low doses ...

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Section: Nf-b Il-8 and Cftr-dependent CLmentioning

confidence: 66%

Section: Potentiating Effects Of Flagellin On Ach-induced Ionic Currementioning

confidence: 70%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Muramatsu

Tamada²,

Nara

et al. 2013

American Journal of Physiology-Lung Cellular and Molecular Phys

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Cystic fibrosis and airway submucosal glands

Inglis

Wilson

2005

Pediatric Pulmonology

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The chronic pulmonary infections and inflammation associated with cystic fibrosis (CF) are responsible for almost all the morbidity and mortality of this disease. Our understanding of the mechanisms that underlie the very early stages of CF lung disease, that result directly from mutations in the CF gene, is relatively poor. However, the demonstration that the predominant sites of expression of the CF gene in normal lungs are the submucosal glands, together with the histological observations showing that hyperplasia of these glands and mucin occlusion of the gland ducts are the earliest signs of disease in the CF lung, suggest that malfunction of the submucosal glands may be an important factor contributing to the early pathophysiology of CF lung disease. This review describes the function of submucosal glands in normal lungs, and the way in which their function may be disrupted in CF and may thus contribute to the early stages of CF lung disease.

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Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane

Aritake

Tamada

Murakami

et al. 2021

Pflugers Arch - Eur J Physiol

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An acquired dysregulation of airway secretion is likely involved in the pathophysiology of chronic bronchitis and chronic obstructive pulmonary disease (COPD). Nowadays, it is widely known that several kinds of long-acting bronchodilators reduce the frequency of COPD exacerbations. However, limited data are available concerning the complementary additive effects on airflow obstruction. Using an optical method and a selective pH indicator, we succeeded in evaluating the gland secretion rate and the pH in swine tracheal membrane. A physiologically relevant concentration of acetylcholine (ACh) 100 nM induced a gradual increase in the amount of gland secretion. Lipopolysaccharides (LPS) accelerated the ACh-induced secretory responses up to around threefold and lowered the pH level significantly. Long-acting β2-agonists (LABAs) including indacaterol (IND), formoterol, and salmeterol restored the LPS-induced changes in both the hypersecretion and acidification. The subsequent addition of the long-acting muscarine antagonist, glycopyrronium, further increased the pH values. Two different inhibitors for cystic fibrosis transmembrane conductance regulator (CFTR), NPPB and CFTRinh172, abolished the IND-mediated pH normalization in the presence of both ACh and ACh + LPS. Both immunofluorescence staining and western blotting analysis revealed that LPS downregulated the abundant expression of CFTR protein. However, IND did not restore the LPS-induced decrease in CFTR expression on Calu-3 cells. These findings suggest that the activation of cAMP-dependent HCO3− secretion through CFTR would be partly involved in the IND-mediated pH normalization in gland secretion and may be suitable for the maintenance of airway defense against exacerbating factors including LPS.

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Differential effect of epidermal growth factor on serous and mucous cells in porcine airway submucosal gland

Cited by 17 publications

References 23 publications

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Flagellin/TLR5 signaling potentiates airway serous secretion from swine tracheal submucosal glands

Cystic fibrosis and airway submucosal glands

Effects of indacaterol on the LPS-evoked changes in fluid secretion rate and pH in swine tracheal membrane

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