Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 100, Issue 6, Pages 1233-1237Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.3HI0416-197R
Keywords
acid sphingomyelinas; acid ceramidase; ceramide bronchial epithelial cells
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Funding
- Shriners Hospitals for Children [85600-CIN-16]
- U.S. National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS) [R01 GM100913, T32 GM08478]
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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.
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