Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma.
Contribution of nitric oxide synthases 1, 2, and 3 to airway hyperresponsiveness and inflammation in a murine model of asthma.
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DOI：
10.1084/jem.189.10.1621
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发表时间：
1999-05-17
期刊：
影响因子：
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通讯作者：
Drazen JM
中科院分区：
文献类型：
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作者：
De Sanctis GT;MacLean JA;Hamada K;Mehta S;Scott JA;Jiao A;Yandava CN;Kobzik L;Wolyniec WW;Fabian AJ;Venugopal CS;Grasemann H;Huang PL;Drazen JM
哮喘是一种慢性疾病，其特征是气道反应性增加和气道炎症。一氧化氮 (NO) 和各种一氧化氮合酶 (NOS) 亚型在人类哮喘中的功能作用存在争议。为了研究 NO 在已建立的过敏性哮喘模型中的作用，对三种已知 NOS 亚型（NOS1、2 和 3）进行靶向删除的小鼠进行了研究。尽管诱导型 (NOS2) 亚型在卵清蛋白 (OVA) 致敏和攻击 (OVA/OVA) 野生型 (WT) 小鼠的肺部显着上调，并且在经过类似处理的 NOS2 缺陷小鼠中检测不到，但这些组之间的气道反应性没有显着差异。与经过类似处理的 NOS1 和 NOS1&3 缺陷型小鼠相比，OVA/OVA 内皮 (NOS3) 缺陷型小鼠对乙酰甲胆碱攻击的反应明显更高。 OVA/OVA 神经元 (NOS1) 缺陷和神经元/内皮 (NOS1&3) 双缺陷小鼠的气道反应性显着低于在类似处理的 NOS2 和 WT 组中观察到的情况。这些发现证明 nNOS 亚型在控制过敏性哮喘模型中气道高反应性的诱导方面具有重要功能。
Asthma is a chronic disease characterized by increased airway responsiveness and airway inflammation. The functional role of nitric oxide (NO) and the various nitric oxide synthase (NOS) isoforms in human asthma is controversial. To investigate the role of NO in an established model of allergic asthma, mice with targeted deletions of the three known isoforms of NOS (NOS1, 2, and 3) were studied. Although the inducible (NOS2) isoform was significantly upregulated in the lungs of ovalbumin (OVA)-sensitized and -challenged (OVA/OVA) wild-type (WT) mice and was undetectable in similarly treated NOS2-deficient mice, airway responsiveness was not significantly different between these groups. OVA/OVA endothelial (NOS3)-deficient mice were significantly more responsive to methacholine challenge compared with similarly treated NOS1 and NOS1&3-deficient mice. Airway responsiveness in OVA/OVA neuronal (NOS1)-deficient and neuronal/endothelial (NOS1&3) double-deficient mice was significantly less than that observed in similarly treated NOS2 and WT groups. These findings demonstrate an important function for the nNOS isoform in controlling the inducibility of airway hyperresponsiveness in this model of allergic asthma.