NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome.
NOX2 protects against progressive lung injury and multiple organ dysfunction syndrome.
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DOI：
10.1152/ajplung.00054.2014
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发表时间：
2014-07
期刊：
影响因子：
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通讯作者：
Laura C. Whitmore;K. Goss;Elizabeth A. Newell;Brieanna Hilkin;Jessica S. Hook;J. Moreland
中科院分区：
文献类型：
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作者：
Laura C. Whitmore;K. Goss;Elizabeth A. Newell;Brieanna Hilkin;Jessica S. Hook;J. Moreland
全身性炎症反应综合征（SIRS）是重症监护病房患者的常见临床症状，可导致并发症，包括多器官功能障碍综合征（MODS）。MODS具有很高的死亡率，目前尚不清楚为什么一些患者会缓解SIRS，而另一些患者会发展为MODS。虽然氧化应激与MODS的发展有关，但最近的一些研究表明，在限制炎症方面需要NADPH氧化酶2 （NOX2）衍生的氧化剂。我们最近在SIRS小鼠模型中证明了NOX2可以防止肺损伤和死亡。在本研究中，我们研究了nox2衍生的氧化剂在SIRS到MODS的进展中的作用。通过小鼠无菌全身性炎症模型，我们观察到gp91(phox-/y) （nox2缺陷）小鼠的疾病和亚急性死亡率明显高于野生型小鼠。细胞分析显示，nox2缺陷小鼠的腹膜和肺部继续有中性粒细胞募集，中性粒细胞和巨噬细胞的激活状态都发生了改变。组织学检查显示，nox2缺失小鼠多器官病理表现为MODS， nox2缺失小鼠肺部多种炎性细胞因子升高。总的来说，这些数据表明NOX2功能可以防止MODS的发展，并且是全身性炎症正常解决所必需的。
Systemic inflammatory response syndrome (SIRS) is a common clinical condition in patients in intensive care units that can lead to complications, including multiple organ dysfunction syndrome (MODS). MODS carries a high mortality rate, and it is unclear why some patients resolve SIRS, whereas others develop MODS. Although oxidant stress has been implicated in the development of MODS, several recent studies have demonstrated a requirement for NADPH oxidase 2 (NOX2)-derived oxidants in limiting inflammation. We recently demonstrated that NOX2 protects against lung injury and mortality in a murine model of SIRS. In the present study, we investigated the role of NOX2-derived oxidants in the progression from SIRS to MODS. Using a murine model of sterile systemic inflammation, we observed significantly greater illness and subacute mortality in gp91(phox-/y) (NOX2-deficient) mice compared with wild-type mice. Cellular analysis revealed continued neutrophil recruitment to the peritoneum and lungs of the NOX2-deficient mice and altered activation states of both neutrophils and macrophages. Histological examination showed multiple organ pathology indicative of MODS in the NOX2-deficient mice, and several inflammatory cytokines were elevated in lungs of the NOX2-deficient mice. Overall, these data suggest that NOX2 function protects against the development of MODS and is required for normal resolution of systemic inflammation.