Rice Teresa C, Seitz Aaron P, Edwards Michael J, Gulbins Erich, Caldwell Charles C
Division of Research, Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, Ohio.
Department of Molecular Biology, University of Essen, Essen, Germany; and.
J Leukoc Biol. 2016 Dec;100(6):1233-1237. doi: 10.1189/jlb.3HI0416-197R. Epub 2016 Jul 14.
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.
尽管接受了抗生素治疗，但伴有肺部铜绿假单胞菌（PA）感染的烧伤患者死亡率高达50%。鞘氨醇由神经酰胺经神经酰胺酶生成，据报道具有抗菌特性。我们观察到烧伤后支气管上皮细胞中鞘氨醇减少，同时神经酰胺增加。接种PA后，与未受伤小鼠相比，这些小鼠的存活率显著降低。然而，当对受伤小鼠用鞘氨醇或中性神经酰胺酶进行预处理后再进行感染时，死亡率和细菌水平显著降低。我们进一步观察到鞘氨醇可直接杀死PA。这些结果共同表明，鞘氨醇减少与烧伤后肺部感染易感性增加有关。通过直接给予鞘氨醇或由中性神经酰胺酶将增加的神经酰胺转化为鞘氨醇来恢复鞘氨醇水平，可降低烧伤后的死亡率并减轻肺部感染。
