De Sanctis G T, MacLean J A, Hamada K, Mehta S, Scott J A, Jiao A, Yandava C N, Kobzik L, Wolyniec W W, Fabian A J, Venugopal C S, Grasemann H, Huang P L, Drazen J M
Pulmonary and Critical Care Divisions, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
J Exp Med. 1999 May 17;189(10):1621-30. doi: 10.1084/jem.189.10.1621.
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.
哮喘是一种以气道反应性增加和气道炎症为特征的慢性疾病。一氧化氮（NO）及各种一氧化氮合酶（NOS）同工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，我们对三种已知NOS同工型（NOS1、2和3）靶向缺失的小鼠进行了研究。虽然在卵清蛋白（OVA）致敏和激发（OVA/OVA）的野生型（WT）小鼠肺中，诱导型（NOS2）同工型显著上调，而在同样处理的NOS2缺陷小鼠中未检测到，但这些组之间的气道反应性并无显著差异。与同样处理的NOS1和NOS1&3缺陷小鼠相比，OVA/OVA内皮型（NOS3）缺陷小鼠对乙酰甲胆碱激发的反应明显更强。OVA/OVA神经元型（NOS1）缺陷小鼠和神经元/内皮型（NOS1&3）双缺陷小鼠的气道反应性明显低于同样处理的NOS2和WT组。这些发现证明了nNOS同工型在控制该过敏性哮喘模型中气道高反应性诱导方面的重要功能。
