Hyperoxia exaggerates bacterial dissemination and lethality in Pseudomonas aeruginosa pneumonia
Hyperoxia exaggerates bacterial dissemination and lethality in Pseudomonas aeruginosa pneumonia
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DOI：
10.1016/j.pupt.2008.12.021
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发表时间：
2009-08-01
影响因子：
3.2
通讯作者：
Yamaguchi, Keizo
中科院分区：
文献类型：
--
作者：
Kikuchi, Yoshiaki;Tateda, Kazuhiro;Yamaguchi, Keizo
高氧对铜绿假单胞菌肺炎小鼠致死率的影响，并在体外和体内研究大环内酯类药物的保护作用。亚致死高氧加速铜绿假单胞菌肺炎小鼠的致死率。在高氧条件下，小鼠肺中的细菌数量没有差异，但肝脏中的细菌数量更高。过滤灭菌培养上清液的细菌诱导肺泡上皮细胞的活力损失，这是夸大了高氧。金属蛋白酶阻断抑制剂或基因破坏细菌导致部分减少细胞毒活性的培养上清液。细菌与亚抑菌浓度的大环内酯类（如阿奇霉素）共培养，可降低培养上清液中的细胞毒性活性。阿奇霉素在高氧肺炎模型中提供了显著的生存益处，这与抑制细菌向肺外器官的传播有关。这些结果表明，高氧是铜绿假单胞菌肺炎细菌传播和致死性的重要辅助因素。我们的数据确定了大环内酯类药物在高氧环境下保护铜绿假单胞菌肺炎患者的潜力。(C)2008年由Elsevier Ltd.出版
Effects of hyperoxia on lethality in mice with Pseudomonas aeruginosa pneumonia were defined, and protective roles of macrolides were examined both in vitro and in vivo. Sub-lethal hyperoxia accelerated lethality of mice with P. aeruginosa pneumonia. Bacterial number was not different in the lungs, but higher in the liver of mice in hyperoxic conditions. Filter-sterilized culture supernatants of bacteria induced loss of viability of alveolar epithelial cells, which was exaggerated in hyperoxia. Metalloprotease blocking by inhibitor or gene-disruption in bacteria resulted in partial reduction of cytotoxic activity in culture supernatants. Co-culture of bacteria with sub-inhibitory concentrations of macrolides, such as azithromycin, reduced cytotoxic activity in the culture supernatants. Azithromycin provided significant survival benefit in hyperoxia-pneumonia model, which was associated with suppression of bacterial dissemination to extra-pulmonary organs. These results suggest that hyperoxia serves as an important cofactor for bacterial dissemination and lethality of P. aeruginosa pneumonia. Our data identify the potential of macrolides to protect individuals with P. aeruginosa pneumonia in the setting of hyperoxia. (C) 2008 Published by Elsevier Ltd.