Rice Teresa C, Pugh Amanda M, Seitz Aaron P, Gulbins Erich, Nomellini Vanessa, Caldwell Charles C
Division of Research, Department of Surgery, University of Cincinnati, Cincinnati, Ohio.
Division of Research, Department of Surgery, University of Cincinnati, Cincinnati, Ohio; Department of Molecular Biology, University of Duisburg-Essen, Essen, Germany.
J Surg Res. 2017 Nov;219:354-359. doi: 10.1016/j.jss.2017.06.042. Epub 2017 Jul 25.
Bacterial lung infection is a leading cause of death for those 65 y or older, often requiring intensive care unit admission and mechanical ventilation, which consumes considerable health care resources. Although administration of antibiotics is the standard of care for bacterial pneumonia, its overuse has led to the emergence of multidrug resistant organisms. Therefore, alternative strategies to help minimize the effects of bacterial pneumonia in the elderly are necessary. As studies have shown that sphingosine (SPH) has inherent bacterial killing properties, our goal was to assess whether it could act as a prophylactic treatment to protect aged mice from pulmonary infection by Pseudomonas aeruginosa.
Aged (51 wk) and young (8 wk) C57Bl/6 mice were used in this study. Pulmonary SPH levels were determined by histology. SPH content of microparticles was quantified using a SPH kinase assay. Pneumonia was induced by intranasally treating mice with 10 Colony Forming Unit (CFU) P aeruginosa. Microparticles were isolated from young mice, whereas some were further incubated with SPH.
We observed that SPH levels are reduced in the bronchial epithelial cells as well as the bronchoalveolar lavage microparticles isolated from aged mice, which correlates with a susceptibility to infection. We demonstrate that SPH or microparticle treatment can protect aged mice from pulmonary P aeruginosa infection. Finally, we observed that enriching microparticles with SPH before treatment eliminated the bacterial load in P aeruginosa-infected aged mice.
These data suggest that prophylactic treatment with SPH could reduce lung bacterial infections for the at-risk elderly population.
细菌性肺部感染是65岁及以上人群的主要死因，常常需要入住重症监护病房并接受机械通气，这消耗了大量医疗资源。尽管使用抗生素是细菌性肺炎的标准治疗方法，但其过度使用已导致多重耐药菌的出现。因此，需要采取替代策略以尽量减少细菌性肺炎对老年人的影响。由于研究表明鞘氨醇（SPH）具有内在的杀菌特性，我们的目标是评估它是否可以作为一种预防性治疗手段，保护老年小鼠免受铜绿假单胞菌引起的肺部感染。
本研究使用了老龄（51周）和年轻（8周）的C57Bl/6小鼠。通过组织学方法测定肺部SPH水平。使用SPH激酶测定法定量微粒中的SPH含量。通过给小鼠鼻内接种10个菌落形成单位（CFU）的铜绿假单胞菌诱导肺炎。从年轻小鼠中分离出微粒，其中一些进一步与SPH孵育。
我们观察到，从老龄小鼠分离的支气管上皮细胞以及支气管肺泡灌洗微粒中的SPH水平降低，这与感染易感性相关。我们证明，SPH或微粒治疗可以保护老龄小鼠免受肺部铜绿假单胞菌感染。最后，我们观察到在治疗前用SPH富集微粒可消除铜绿假单胞菌感染的老龄小鼠中的细菌负荷。
这些数据表明，用SPH进行预防性治疗可以减少高危老年人群的肺部细菌感染。
