Elicitation of reactive oxygen species in Chlamydia pneumoniae-stimulated macrophages:: a Ca2+-dependent process involving simultaneous activation of NADPH oxidase and cytochrome oxidase genes
Elicitation of reactive oxygen species in Chlamydia pneumoniae-stimulated macrophages:: a Ca2+-dependent process involving simultaneous activation of NADPH oxidase and cytochrome oxidase genes
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DOI：
10.1007/s00430-004-0223-4
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发表时间：
2005-01-01
影响因子：
5.4
通讯作者：
Adedokun, OO
中科院分区：
文献类型：
--
作者：
Azenabor, AA;Yang, S;Adedokun, OO
肺炎衣原体是一种与动脉粥样硬化的发生和进展有关的呼吸道病原体，尽管巨噬细胞会产生活性氧（ROS），但已知它会感染巨噬细胞并在巨噬细胞中存活。为了深入了解感染肺炎衣原体的巨噬细胞中 ROS 的产生，并探索影响其最终水平和效果的因素，我们研究了 NADPH 氧化酶和细胞色素氧化酶途径在 ROS 产生和调节中的作用。我们还确定了 Ca2+ 信号传导在此过程中的操作作用。肺炎衣原体刺激的巨噬细胞通过上调 NADPH 氧化酶和细胞色素 c 氧化酶活性表现出 ROS 的早期释放。增加肺炎衣原体的剂量会导致这些酶的基因表达增加，同时伴随着其基因产物的显着上调，这意味着转录和翻译过程可能分别被激活。游离 Ca2+ 水平的变化、跨质膜的流入以及从细胞内储存到细胞质的流出都对巨噬细胞中 ROS 生成途径表现出显着的调节作用。观察到的事件显示依赖于肺炎衣原体与巨噬细胞 CD14 受体的结合。这里报告的数据表明，感染肺炎衣原体的巨噬细胞通过膜相关的 NADPH 氧化酶产生 ROS，其氧化磷酸化水平取决于 Ca2+ 流入信号。
Chlamydia pneumoniae, a respiratory pathogen implicated in the development and progress of atherosclerosis, is known to infect and survive in macrophages, despite macrophage producing reactive oxygen species (ROS). To gain insight into ROS generation in macrophages infected with C. pneumoniae and to explore factors accounting for their final levels and effect, we investigated the role of NADPH oxidase and cytochrome oxidase pathways in the production and modulation of ROS. We also determined the operational role of Ca2+ signaling in the process. Macrophages stimulated with C. pneumoniae exhibit early release of ROS via up-regulation of NADPH oxidase and cytochrome c oxidase activities. Increasing the dose or C. pneumoniae led to an increase in the expression of these enzymes' gene production, which was accompanied by a significant up-regulation of their gene products, implying a probable activation of transcriptional and translational processes, respectively. The change in levels of free Ca2+, influx across plasma membrane and efflux from intracellular store into cytosol all exhibited a significant regulatory role on the ROS generation pathways in macrophages. The observed events were shown to be dependent on binding of C. pneumoniae to CD14 receptors of macrophages. The data reported here imply that macrophages infected with C. pneumoniae produce ROS through membrane-associated NADPH oxidase with oxidative phosphorylation levels depending on Ca2+ influx signals.