> Detailanzeige

Simonin, Juliette; Bille, Emmanuelle; Crambert, Gilles; Noel, Sabrina; Dreano, Elise; Edwards, Aurélie; Hatton, Aurélie; Pranke, Iwona; Villeret, Bérengère; Cottart, Charles-Henry; Vrel, Jean-Patrick; Urbach, Valérie; Baatallah, Nesrine; Hinzpeter, Alexandre; Golec, Anita; Touqui, Lhousseine; Nassif, Xavier; Galietta, Luis J. V; Planelles, Gabrielle; Sallenave, Jean-Michel; Edelman, Aleksander; Sermet-Gaudelus, Isabelle

Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis

Literatur-
verwaltung

Zur
Merkliste

Lösche von
Merkliste

Per Whatsapp teilen

Schließen

Merkliste



Sie können Bookmarks mittels Listen verwalten, loggen Sie sich dafür bitte in Ihr SLUB Benutzerkonto ein.
  • Medientyp: E-Artikel
  • Titel: Airway surface liquid acidification initiates host defense abnormalities in Cystic Fibrosis
  • Beteiligte: Simonin, Juliette; Bille, Emmanuelle; Crambert, Gilles; Noel, Sabrina; Dreano, Elise; Edwards, Aurélie; Hatton, Aurélie; Pranke, Iwona; Villeret, Bérengère; Cottart, Charles-Henry; Vrel, Jean-Patrick; Urbach, Valérie; Baatallah, Nesrine; Hinzpeter, Alexandre; Golec, Anita; Touqui, Lhousseine; Nassif, Xavier; Galietta, Luis J. V; Planelles, Gabrielle; Sallenave, Jean-Michel; Edelman, Aleksander; Sermet-Gaudelus, Isabelle
  • Erschienen: Springer Science and Business Media LLC, 2019
  • Erschienen in: Scientific Reports
  • Sprache: Englisch
  • DOI: 10.1038/s41598-019-42751-4
  • ISSN: 2045-2322
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Cystic fibrosis (CF) is caused by defective Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) protein. Morbidity is mainly due to early airway infection. We hypothesized that <jats:italic>S. aureus</jats:italic> clearance during the first hours of infection was impaired in CF human Airway Surface Liquid (ASL) because of a lowered pH. The ASL pH of human bronchial epithelial cell lines and primary respiratory cells from healthy controls (WT) and patients with CF was measured with a pH microelectrode. The antimicrobial capacity of airway cells was studied after <jats:italic>S. aureus</jats:italic> apical infection by counting surviving bacteria. ASL was significantly more acidic in CF than in WT respiratory cells. This was consistent with a defect in bicarbonate secretion involving CFTR and SLC26A4 (pendrin) and a persistent proton secretion by ATP12A. ASL demonstrated a defect in <jats:italic>S. aureus</jats:italic> clearance which was improved by pH normalization. Pendrin inhibition in WT airways recapitulated the CF airway defect and increased <jats:italic>S. aureus</jats:italic> proliferation. ATP12A inhibition by ouabain decreased bacterial proliferation. Antimicrobial peptides LL-37 and hBD1 demonstrated a pH-dependent activity. Normalizing ASL pH might improve innate airway defense in newborns with CF during onset <jats:italic>of S. aureus</jats:italic> infection. Pendrin activation and ATP12A inhibition could represent novel therapeutic strategies to normalize pH in CF airways.</jats:p>
  • Zugangsstatus: Freier Zugang