Singlet oxygen is essential for neutrophil extracellular trap formation
Singlet oxygen is essential for neutrophil extracellular trap formation
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DOI：
10.1016/j.bbrc.2011.08.052
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发表时间：
2011-09-16
影响因子：
3.1
通讯作者：
Yamashita, Kouhei
中科院分区：
文献类型：
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作者：
Nishinaka, Yoko;Arai, Toshiyuki;Yamashita, Kouhei
结合入侵微生物的中性粒细胞胞外陷阱（NET）对于宿主先天防御至关重要。越来越多的证据表明 NET 在感染性和炎症性疾病发病机制中的重要性，但 NET 形成的机制仍不清楚。先前对慢性肉芽肿病 (CGD) 患者的中性粒细胞的观察发现，这些患者的 NADPH 氧化酶 (Nox) 缺陷且无法产生活性氧 (ROS)，结果表明 ROS 有助于 NET 的形成。然而，活性物种尚未确定。在这项研究中，我们发现单线态氧（ROS 之一）在佛波醇肉豆蔻酸酯乙酸酯刺激后介导 Nox 依赖性 NET 形成。我们还发现，单线态氧本身可以通过在 CGD 中性粒细胞以及健康中性粒细胞中与卟吩姆钠 (Photofrin) 产生单线态氧的独特系统诱导 NET 形成。这与 Nox 激活无关。这些结果表明单线态氧对于 NET 的形成至关重要，并为传染病和炎症性疾病的发病机制提供了新的见解。 (C) 2011 Elsevier Inc. 保留所有权利。
Neutrophil extracellular traps (NETs) that bind invading microbes are pivotal for innate host defense. There is a growing body of evidence for the significance of NETs in the pathogenesis of infectious and inflammatory diseases, but the mechanism of NET formation remains unclear. Previous observation in neutrophils of chronic granulomatous disease (CGD) patients, which defect NADPH oxidase (Nox) and fail to produce reactive oxygen species (ROS), revealed that ROS contributed to the formation of NETs. However, the active species were not identified. In this study, we discovered that singlet oxygen, one of the ROS, mediated Nox-dependent NET formation upon stimulation with phorbol myristate acetate. We also revealed that singlet oxygen itself could induce NET formation by a distinct system generating singlet oxygen with porfimer sodium (Photofrin) in CGD neutrophils, as well as healthy neutrophils. This was independent of Nox activation. These results show that singlet oxygen is essential for NET formation, and provide novel insights into the pathogenesis of infectious and inflammatory diseases. (C) 2011 Elsevier Inc. All rights reserved.