Dokument-ID Dokumenttyp Verfasser/Autoren Herausgeber Haupttitel Abstract Auflage Verlagsort Verlag Erscheinungsjahr Seitenzahl Schriftenreihe Titel Schriftenreihe Bandzahl ISBN Quelle der Hochschulschrift Konferenzname Quelle:Titel Quelle:Jahrgang Quelle:Heftnummer Quelle:Erste Seite Quelle:Letzte Seite URN DOI Abteilungen OPUS4-37594 Wissenschaftlicher Artikel Pewzner-Jung, Yael; Tabazavareh, Shaghayegh Tavakoli; Grassme, Heike; Becker, Katrin Anne; Japtok, Lukasz; Steinmann, Joerg; Joseph, Tammar; Lang, Stephan; Tuemmler, Burkhard; Schuchman, Edward H.; Lentsch, Alex B.; Kleuser, Burkhard; Edwards, Michael J.; Futerman, Anthony H.; Gulbins, Erich Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa Cystic fibrosis patients and patients with chronic obstructive pulmonary disease, trauma, burn wound, or patients requiring ventilation are susceptible to severe pulmonary infection by Pseudomonas aeruginosa. Physiological innate defense mechanisms against this pathogen, and their alterations in lung diseases, are for the most part unknown. We now demonstrate a role for the sphingoid long chain base, sphingosine, in determining susceptibility to lung infection by P.aeruginosa. Tracheal and bronchial sphingosine levels were significantly reduced in tissues from cystic fibrosis patients and from cystic fibrosis mouse models due to reduced activity of acid ceramidase, which generates sphingosine from ceramide. Inhalation of mice with sphingosine, with a sphingosine analog, FTY720, or with acid ceramidase rescued susceptible mice from infection. Our data suggest that luminal sphingosine in tracheal and bronchial epithelial cells prevents pulmonary P.aeruginosa infection in normal individuals, paving the way for novel therapeutic paradigms based on inhalation of acid ceramidase or of sphingoid long chain bases in lung infection. Hoboken Wiley-Blackwell 2014 10 EMBO molecular medicine 6 9 1205 1214 10.15252/emmm.201404075 Institut für Ernährungswissenschaft