title: Frontline Science: Sphingosine rescues burn-injured mice from pulmonary Pseudomonas aeruginosa infection.
abstract: Burn patients with concomitant pulmonary Pseudomonas aeruginosa (PA) infection have mortality rates as high as 50%, despite antibiotic therapy. Sphingosine is generated from ceramide via ceramidase and has been reported to have antimicrobial properties. We observed a reduction in sphingosine and a concurrent increase in ceramide in bronchial epithelial cells after burn injury. After PA inoculation, these mice had a significant decrease in survival compared to noninjured mice. However, when injured mice were pretreated with sphingosine or neutral ceramidase and subsequently infected, mortality and bacterial levels were robustly reduced. We further observed that sphingosine directly kills PA. Together, these results demonstrate that reduction in sphingosine is associated with an increased susceptibility to pulmonary infection after burn injury. Restoration of sphingosine levels through direct sphingosine administration or conversion of the increased ceramide to sphingosine by neutral ceramidase reduces mortality and mitigates pulmonary infection after burn injury.
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Teresa C
authors.initials: TC
authors.lastname: Rice
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Seitz
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Edwards
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.|Department of Molecular Biology, University of Essen, Essen, Germany; and.|Department of Research, Shriners Hospitals for Children, Cincinnati, Ohio.
authors.forename: Erich
authors.initials: E
authors.lastname: Gulbins
authors.affiliation: Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio; charles.caldwell@uc.edu.|Department of Research, Shriners Hospitals for Children, Cincinnati, Ohio.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Caldwell
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002056:Burns / Q000150:complications*; D002518:Ceramides / Q000378:metabolism; D016207:Cytokines / Q000032:analysis; D004198:Disease Susceptibility; D004353:Drug Evaluation, Preclinical; D008168:Lung / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D008297:Male; D051379:Mice; D055576:Neutral Ceramidase / Q000627:therapeutic use; D018410:Pneumonia, Bacterial / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology / Q000473:pathology; D011552:Pseudomonas Infections / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000627:therapeutic use; D013110:Sphingosine / Q000627:therapeutic use*
chemical_list: D002518:Ceramides; D016207:Cytokines; D011994:Recombinant Proteins; D055576:Neutral Ceramidase; D013110:Sphingosine
keywords: acid ceramidase; acid sphingomyelinas; ceramide bronchial epithelial cells