title: Modulation of epithelial sodium channel activity by lipopolysaccharide in alveolar type II cells: involvement of purinergic signaling.
abstract: 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.
authors.affiliation: Département de Médecine, Centre de Recherche, Centre Hospitalier de l'Université de Montréal-Hôtel-Dieu, 3840 St. Urbain, Montréal, PQ, Canada.
authors.forename: Emilie
authors.initials: E
authors.lastname: Boncoeur
authors.forename: Valérie
authors.initials: V
authors.lastname: Tardif
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Tessier
authors.forename: Frédéric
authors.initials: F
authors.lastname: Morneau
authors.forename: Jacynthe
authors.initials: J
authors.lastname: Lavoie
authors.forename: Erik
authors.initials: E
authors.lastname: Gendreau-Berthiaume
authors.forename: Ryszard
authors.initials: R
authors.lastname: Grygorczyk
authors.forename: André
authors.initials: A
authors.lastname: Dagenais
authors.forename: Yves
authors.initials: Y
authors.lastname: Berthiaume
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D056809:Alveolar Epithelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D053503:Epithelial Sodium Channels / Q000378:metabolism*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008954:Models, Biological; D011493:Protein Kinase C / Q000378:metabolism; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011983:Receptors, Purinergic / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D012964:Sodium / Q000378:metabolism; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors; D014357:Trypsin / Q000494:pharmacology; D010738:Type C Phospholipases / Q000378:metabolism
chemical_list: D053503:Epithelial Sodium Channels; D008070:Lipopolysaccharides; D021122:Protein Subunits; D011983:Receptors, Purinergic; D013498:Suramin; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D011493:Protein Kinase C; D010738:Type C Phospholipases; D014357:Trypsin