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EMBO Mol Med. 2014 Sep;6(9):1205-14. doi: 10.15252/emmm.201404075.

Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa.

Author information

1
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel erich.gulbins@uni-due.de yael.pewzner-jung@weizmann.ac.il.
2
Department of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
3
Department of Nutritional Science, University of Potsdam, Potsdam, Germany.
4
Department of Microbiology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
5
Department of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel.
6
Department of Otorhinolaryngology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
7
Klinische Forschergruppe, OE 6710, Medizinische Hochschule Hannover, Hannover, Germany.
8
Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
9
Department of Surgery, University of Cincinnati, Cincinnati, OH, USA.
10
Department of Molecular Biology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany Department of Surgery, University of Cincinnati, Cincinnati, OH, USA erich.gulbins@uni-due.de yael.pewzner-jung@weizmann.ac.il.

Abstract

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.

KEYWORDS:

Pseudomonas aeruginosa; cystic fibrosis; long chain base; lung infection; sphingosine

PMID:
25085879
PMCID:
PMC4197866
DOI:
10.15252/emmm.201404075
[Indexed for MEDLINE]
Free PMC Article

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