Frontline Science: Sphingosine rescues burn-injured mice from pulmonary Pseudomonas aeruginosa infection
Frontline Science: Sphingosine rescues burn-injured mice from pulmonary Pseudomonas aeruginosa infection
复制标题
DOI：
10.1189/jlb.3hi0416-197r
复制
发表时间：
2016-12-01
影响因子：
5.5
通讯作者：
Caldwell, Charles C.
中科院分区：
文献类型：
--
作者：
Rice, Teresa C.;Seitz, Aaron P.;Caldwell, Charles C.
烧伤患者合并肺部绿脓杆菌（PA）感染的死亡率高达50%，尽管抗生素治疗。鞘氨醇是由神经酰胺通过神经酰胺酶产生的，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，神经酰胺同时增加。PA接种后，这些小鼠的存活率与未受伤小鼠相比显著降低。然而，当受伤的小鼠用鞘氨醇或中性神经酰胺酶预处理并随后感染时，死亡率和细菌水平显著降低。我们进一步观察到鞘氨醇直接杀死PA。总之，这些结果表明，鞘氨醇的减少与烧伤后肺部感染的易感性增加有关。通过直接给予鞘氨醇或通过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。
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.