Modulation of epithelial sodium channel activity by lipopolysaccharide in alveolar type II cells: Involvement of purinergic signaling

Département de Médecine, Centre de Recherche, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, 3840 St. Urbain, Montréal, PQ, Canada.
AJP Lung Cellular and Molecular Physiology (Impact Factor: 4.08). 12/2009; 298(3):L417-26. DOI: 10.1152/ajplung.00170.2009
Source: PubMed


Pseudomonas aeruginosa is a gram-negative bacterium that causes chronic infection in cystic fibrosis patients. We reported recently that P. aeruginosa modulates epithelial Na(+) channel (ENaC) expression in experimental chronic pneumonia models. For this reason, we tested whether LPS from P. aeruginosa alters ENaC expression and activity in alveolar epithelial cells. We found that LPS induces a approximately 60% decrease of ENaC apical current without significant changes in intracellular ENaC or surface protein expression. Because a growing body of evidence reports a key role for extracellular nucleotides in regulation of ion channels, we evaluated the possibility that modulation of ENaC activity by LPS involves extracellular ATP signaling. We found that alveolar epithelial cells release ATP upon LPS stimulation and that pretreatment with suramin, a P2Y(2) purinergic receptor antagonist, inhibited the effect of LPS on ENaC. Furthermore, ET-18-OCH3, a PLC inhibitor, and Go-6976, a PKC inhibitor, were able to partially prevent ENaC inhibition by LPS, suggesting that the actions of LPS on ENaC current were mediated, in part, by the PKC and PLC pathways. Together, these findings demonstrate an important role of extracellular ATP signaling in the response of epithelial cells to LPS.

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Available from: Emilie Boncoeur, Jul 16, 2015
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    • "Several factors have been shown to modulate ENaC expression and activity in the lungs, including purinergic signaling [9–11], glucocorticoid [12–16], protease activation [10,17,18] and membrane recycling or lysosomal degradation of the channel [19]. Since transepithelial Na+ transport involves activity of the Na/K-ATPase expression at the basolateral side, factors that regulate the sodium pump or its membrane insertion have an impact on the Na+ transport system [14,20]. "
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    • "LPS has also been reported to regulate airway epithelial ion transport. LPS from P. aeruginosa inhibits sodium absorption via ENaC in mammalian alveolar epithelial cells [4]. In contrast, LPS from Salmonella enterica stimulated sodium absorption by increasing Na/K ATPase expression in guinea-pig tracheal epithelium [5]. "
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