Inhibition of Na<sup>+</sup> Transport in Lung Epithelial Cells by Respiratory Syncytial Virus Infection

Chen, Lan; Song, Weifeng; Davis, Ian C.; Shrestha, Kedar; Schwiebert, Erik M.; Sullender, Wayne M.; Matalon, Sadis

doi:10.1165/rcmb.2008-0034oc

Cited by 48 publications

(50 citation statements)

References 37 publications

(53 reference statements)

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“…This suggests that P2Y 2 receptor antagonists may be useful for the treatment of severe respiratory syncytial virus bronchiolitis. Respiratory syncytial virus infection causes fluid accumulation and decreased Na ϩ transfer across respiratory epithelial cells, probably via UTP released from epithelial cells (Chen et al, 2009). In addition, influenza A virus inhibits alveolar fluid clearance in BALB/C mice (Wolk et al, 2008).…”

Section: Airway Infectionsmentioning

confidence: 99%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

173

158

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Section: Airway Infectionsmentioning

confidence: 99%

Purinergic Signaling in the Airways

Burnstock

Brouns²,

Adriaensen³

et al. 2012

Pharmacol Rev

173

158

View full text Add to dashboard Cite

“…Cells were mounted in Ussing chambers, and shortcircuit currents (I sc ) and transepithelial resistances were measured before and after addition of amiloride (10 mM), forskolin (10 mM), and glibenclamide (400 mM) in the apical compartments (21,23,24).…”

Section: Short-circuit Currents Across Atii Cellsmentioning

confidence: 99%

Inter-α-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in ΔF508 Mice

Lazrak

Jurkuvenaite

Ness

et al. 2014

Am J Respir Cell Mol Biol

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Increased activity of lung epithelial sodium channels (ENaCs) contributes to the pathophysiology of cystic fibrosis (CF) by increasing the rate of epithelial lining fluid reabsorption. Intera-inhibitor (IaI), a serum protease inhibitor, may decrease ENaC activity by preventing its cleavage by serine proteases. High concentrations of IaI were detected in the bronchoalveolar lavage fluid (BALF) of children with CF and lower airway diseases. IaI decreased amiloride-sensitive (I ENaC ) but not cAMP-activated Cl 2 currents across confluent monolayers of rat ATII, and mouse nasal epithelial cells grew in primary culture by 45 and 25%, respectively. Changes in I ENaC by IaI in ATII cells were accompanied by increased levels of uncleaved (immature) surface a-ENaC. IaI increased airway surface liquid depth overlying murine nasal epithelial cells to the same extent as amiloride, consistent with ENaC inhibition. Incubation of lung slices from C57BL/6, those lacking phenylalanine at position 508 (ΔF508), or CF transmembrane conductance regulator knockout mice with IaI for 3 hours decreased the open probability of their ENaC channels by 50%. ΔF508 mice had considerably higher levels the amiloride-sensitive fractions of ENaC nasal potential difference (ENaC-NPD) than wild-type littermates and only background levels of IaI in their BALF. A single intranasal instillation of IaI decreased their ENaC-NPD 24 hours later by 25%. In conclusion, we show that IaI is present in the BALF of children with CF, is an effective inhibitor of ENaC proteolysis, and decreases ENaC activity in lung epithelial cells of ΔF508 mice.

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“…ATII cell monolayers were mounted in Ussing chambers at 1 hour or 24 hours after exposure to Cl 2 , as previously described (22,23).…”

Section: Measurements Of Atii Cell Short-circuit Currents and Transepmentioning

confidence: 99%

Regulation of Alveolar Epithelial Na⁺ Channels by ERK1/2 in Chlorine-Breathing Mice

Lazrak¹,

Chen²,

Jurkuvenaite³

et al. 2012

Am J Respir Cell Mol Biol

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The mechanisms by which the exposure of mice to Cl 2 decreases vectorial Na 1 transport and fluid clearance across their distal lung spaces have not been elucidated. We examined the biophysical, biochemical, and physiological changes of rodent lung epithelial Na 1 channels (ENaCs) after exposure to Cl 2 , and identified the mechanisms involved. We measured amiloride-sensitive short-circuit currents (I amil ) across isolated alveolar Type II (ATII) cell monolayers and ENaC single-channel properties by patching ATII and ATI cells in situ. a-ENaC, g-ENaC, total and phosphorylated extracellular signalrelated kinase (ERK)1/2, and advanced products of lipid peroxidation in ATII cells were measured by Western blot analysis. Concentrations of reactive intermediates were assessed by electron spin resonance (ESR). Amiloride-sensitive Na 1 channels with conductances of 4.5 and 18 pS were evident in ATI and ATII cells in situ of air-breathing mice. At 1 hour and 24 hours after exposure to Cl 2 , the open probabilities of these two channels decreased. This effect was prevented by incubating lung slices with inhibitors of ERK1/2 or of proteasomes and lysosomes. The exposure of ATII cell monolayers to Cl 2 increased concentrations of reactive intermediates, leading to ERK1/2 phosphorylation and decreased I amil and a-ENaC concentrations at 1 hour and 24 hours after exposure. The administration of antioxidants to ATII cells before and after exposure to Cl 2 decreased concentrations of reactive intermediates and ERK1/2 activation, which mitigated the decrease in I amil and ENaC concentrations. The reactive intermediates formed during and after exposure to Cl 2 activated ERK1/2 in ATII cells in vitro and in vivo, leading to decreased ENaC concentrations and activity.

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Inhibition of Na⁺ Transport in Lung Epithelial Cells by Respiratory Syncytial Virus Infection

Cited by 48 publications

References 37 publications

Purinergic Signaling in the Airways

Purinergic Signaling in the Airways

Inter-α-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in ΔF508 Mice

Regulation of Alveolar Epithelial Na⁺ Channels by ERK1/2 in Chlorine-Breathing Mice

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Inhibition of Na+ Transport in Lung Epithelial Cells by Respiratory Syncytial Virus Infection

Cited by 48 publications

References 37 publications

Purinergic Signaling in the Airways

Purinergic Signaling in the Airways

Inter-α-Inhibitor Blocks Epithelial Sodium Channel Activation and Decreases Nasal Potential Differences in ΔF508 Mice

Regulation of Alveolar Epithelial Na+ Channels by ERK1/2 in Chlorine-Breathing Mice

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Resources

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Inhibition of Na⁺ Transport in Lung Epithelial Cells by Respiratory Syncytial Virus Infection

Regulation of Alveolar Epithelial Na⁺ Channels by ERK1/2 in Chlorine-Breathing Mice