Open AccessSphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa
Author(s) -
PewznerJung Yael,
Tavakoli Tabazavareh Shaghayegh,
Grassmé Heike,
Becker Katrin Anne,
Japtok Lukasz,
Steinmann Jörg,
Joseph Tammar,
Lang Stephan,
Tuemmler Burkhard,
Schuchman Edward H,
Lentsch Alex B,
Kleuser Burkhard,
Edwards Michael J,
Futerman Anthony H,
Gulbins Erich
Publication year - 2014
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.201404075
Subject(s) - sphingosine , cystic fibrosis , ceramide , pseudomonas aeruginosa , sphingolipid , lung , immunology , medicine , biology , microbiology and biotechnology , biochemistry , bacteria , apoptosis , genetics , receptor
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, FTY 720, 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.