Frontline Science: Sphingosine rescues burn‐injured mice from pulmonary Pseudomonas aeruginosa infection. Issue 6 (14th July 2016)

• Record Type: Journal Article
• Authors: Rice, Teresa C.; Seitz, Aaron P.; Edwards, Michael J.; Gulbins, Erich; Caldwell, Charles C.
• Is Part Of: Journal of leukocyte biology. Volume 100:Issue 6(2016)
• Page Start: 1233
• Page End: 1237
• Publication Date: 2016-07-14
• Subjects: acid sphingomyelinas -- acid ceramidase -- ceramide bronchial epithelial cells; Leucocytes -- Periodicals; Reticulo-endothelial system -- Periodicals; 571.96
• DOI: 10.1189/jlb.3HI0416-197R
• Languages: English
• ISSNs: 0741-5400

Abstract

Abstract : Restoration of SPH levels through direct SPH administration, or conversion of increased ceramide to SPH by NC, reduces mortality and mitigates pulmonary infection after burn injury. 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.