Sphingoid long chain bases prevent lung infection by Pseudomonas aeruginosa

被引：107

作者：

Pewzner-Jung, Yael ^{[1
]}

Tabazavareh, Shaghayegh Tavakoli ^{[2
]}

Grassme, Heike ^{[2
]}

Becker, Katrin Anne ^{[2
]}

Japtok, Lukasz ^{[3
]}

Steinmann, Joerg ^{[4
]}

Joseph, Tammar ^{[1
]}

Lang, Stephan ^{[5
]}

Tuemmler, Burkhard ^{[6
]}

Schuchman, Edward H. ^{[7
]}

Lentsch, Alex B. ^{[8
]}

Kleuser, Burkhard ^{[3
]}

Edwards, Michael J. ^{[8
]}

Futerman, Anthony H. ^{[1
]}

Gulbins, Erich ^{[2
,8
]}

机构：

[1] Weizmann Inst Sci, Dept Biol Chem, IL-76100 Rehovot, Israel

[2] Univ Duisburg Essen, Univ Hosp Essen, Dept Mol Biol, Essen, Germany

[3] Univ Potsdam, Dept Nutr Sci, Potsdam, Germany

[4] Univ Duisburg Essen, Univ Hosp Essen, Dept Microbiol, Essen, Germany

[5] Univ Duisburg Essen, Univ Hosp Essen, Dept Otorhinolaryngol, Essen, Germany

[6] Hannover Med Sch, Klin Forschergrp, D-30623 Hannover, Germany

[7] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA

[8] Univ Cincinnati, Dept Surg, Cincinnati, OH 45267 USA

来源：

EMBO MOLECULAR MEDICINE | 2014年 / 6卷 / 09期

关键词：

cystic fibrosis; long chain base; lung infection; Pseudomonas aeruginosa; sphingosine; CYSTIC-FIBROSIS LUNG; ACID SPHINGOMYELINASE; STAPHYLOCOCCUS-AUREUS; CERAMIDE; INFLAMMATION; BACTEREMIA; RESISTANCE; DISEASE;

D O I：

10.15252/emmm.201404075

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页码：1205 / 1214

页数：10

共 25 条

[1] Decreased levels of sphingosine, a natural antimicrobial agent, may be associated with vulnerability of the stratum corneum from patients with atopic dermatitis to colonization by Staphylococcus aureus [J].