Maeda Tsuneharu, Kimura Soichiro, Matsumoto Tetsuya, Tanabe Yoshinari, Gejyo Fumitake, Yamaguchi Keizo
Department of Microbiology and Infectious Diseases, Toho University Faculty of Medicine, Tokyo 143-8540, Japan.
BMC Res Notes. 2011 Apr 6;4:107. doi: 10.1186/1756-0500-4-107.
Oxygen supplementation is commonly given to the patients with severe pneumonia including Legionella disease. Recent data suggested that apoptosis may play an important role, not only in the pathogenesis of Legionella pneumonia, but also in oxygen-induced tissue damage. In the present study, the lethal sensitivity to Legionella pneumonia were compared in the setting of hyperoxia between wild-type and Fas-deficient mice.
C57BL/6 mice and B6.MRL-Faslpr mice characterized with Fas-deficiency were used in this study. After intratracheal administration of L. pneumophila, mice were kept in hyperoxic conditions (85-90% O2 conc.) in an airtight chamber for 3 days. Bone-marrow derived macrophages infected with L. pneumophila were also kept in hyperoxic conditions. Caspase activity and cytokine production were determined by using commercially available kits. Smaller increases of several apoptosis markers, such as caspase-3 and -8, were demonstrated in Fas-deficient mice, even though the bacterial burdens in Fas-deficient and wild type mice were similar. Bone-marrow derived macrophages from Fas-deficient mice were shown to be more resistant to Legionella-induced cytotoxicity than those from wild-type mice under hyperoxia.
These results demonstrated that Fas-mediated signaling and apoptosis may be a crucial factor in the pathogenesis of Legionella pneumonia in the setting of hyperoxia.
对于包括军团菌病在内的重症肺炎患者，通常会给予吸氧治疗。近期数据表明，细胞凋亡不仅可能在军团菌肺炎的发病机制中起重要作用，还可能在氧诱导的组织损伤中起重要作用。在本研究中，比较了野生型和Fas缺陷型小鼠在高氧环境下对军团菌肺炎的致死敏感性。
本研究使用了具有Fas缺陷特征的C57BL/6小鼠和B6.MRL-Faslpr小鼠。经气管内给予嗜肺军团菌后，将小鼠置于密闭舱内的高氧环境（氧气浓度85 - 90%）中3天。感染嗜肺军团菌的骨髓来源巨噬细胞也置于高氧环境中。使用市售试剂盒测定半胱天冬酶活性和细胞因子产生情况。尽管Fas缺陷型小鼠和野生型小鼠体内的细菌载量相似，但在Fas缺陷型小鼠中，几种凋亡标志物（如半胱天冬酶-3和-8）的增加幅度较小。在高氧环境下，Fas缺陷型小鼠的骨髓来源巨噬细胞比野生型小鼠的骨髓来源巨噬细胞对军团菌诱导的细胞毒性更具抗性。
这些结果表明，Fas介导的信号传导和细胞凋亡可能是高氧环境下军团菌肺炎发病机制中的关键因素。
