Yael Pewzner-Jung, Shaghayegh Tavakoli Tabazavareh, Heike Grassme, Katrin Anne Becker, Lukasz Japtok, Joerg Steinmann, Tammar Joseph, Stephan Lang, Burkhard Tuemmler, Edward H. Schuchman, Alex B. Lentsch, Burkhard Kleuser, Michael J. Edwards, Anthony H. Futerman, Erich Gulbins
- 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 paradigmsCystic 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.…
MetadatenVerfasserangaben: | Yael Pewzner-Jung, Shaghayegh Tavakoli Tabazavareh, Heike Grassme, Katrin Anne BeckerORCiDGND, Lukasz JaptokGND, Joerg Steinmann, Tammar Joseph, Stephan Lang, Burkhard Tuemmler, Edward H. Schuchman, Alex B. Lentsch, Burkhard KleuserORCiDGND, Michael J. Edwards, Anthony H. Futerman, Erich GulbinsORCiDGND |
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DOI: | https://doi.org/10.15252/emmm.201404075 |
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ISSN: | 1757-4676 |
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ISSN: | 1757-4684 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/25085879 |
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Titel des übergeordneten Werks (Englisch): | EMBO molecular medicine |
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Verlag: | Wiley-Blackwell |
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Verlagsort: | Hoboken |
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Publikationstyp: | Wissenschaftlicher Artikel |
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Sprache: | Englisch |
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Jahr der Erstveröffentlichung: | 2014 |
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Erscheinungsjahr: | 2014 |
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Datum der Freischaltung: | 27.03.2017 |
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Freies Schlagwort / Tag: | Pseudomonas aeruginosa; cystic fibrosis; long chain base; lung infection; sphingosine |
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Band: | 6 |
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Ausgabe: | 9 |
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Seitenanzahl: | 10 |
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Erste Seite: | 1205 |
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Letzte Seite: | 1214 |
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Fördernde Institution: | German-Israeli-Foundation [1105-69.11/2010]; DFG grant [335/16-2];
BMBF-grant [0315827B]; NIH grant [DK25809] |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access |
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