EXTRACELLULAR SUPEROXIDE DISMUTASE IN AIRWAY AND PULMONARY VASCULAR BIOLOGY

抗氧化酶在肺气道和血管调节中的作用 将对疾病进行评估。其中一个最重要的发现， 该赠款的前一个供资期是，细胞外形式的 超氧化物歧化酶（EC-SOD）是一种在大肠杆菌中高度表达的蛋白质， 肺它被发现主要定位于细胞外 气道和肺内平滑肌细胞周围的空间 脉管系统有待检验的假设是，EC-SOD起关键作用， 调节一氧化氮（NO.）在肺部。的 EC-SOD调节NO活性的可能机制包括 清除O2-，从而阻止O2-与NO反应。的 一氧化氮合酶的分布和物理关系（The NO的酶源）。和EC-SOD在肺气道和 将确定肺脉管系统。体外和体内动物 模型将被用于证明EC-SOD在调节气道中的作用 和肺血管张力具体目标是：1）创建工具， EC-SOD在动物模型中的研究， 2）免疫定位气道内EC-SOD， 肺血管系统，3）免疫定位气道中的一氧化氮合酶 研究气道支气管扩张的机制 肺血管张力调节机制的研究 调控这些拟议的研究预计将证明EC-SOD 在调节气道和血管张力方面起着关键作用， 肺。通过证明这种酶的生理重要性，我们 希望找到新的药物治疗方法， 同时涉及气道高反应性和肺血管 反应过度

The role of antioxidant enzymes in modulating lung airway and vascular diseases will be evaluated. One of the most important findings during the prior funding period of this grant was that the extracellular form of superoxide dismutase (EC-SOD) is a protein uniquely highly expressed in the lung. It was found to be primarily localized in the extracellular spaces surrounding smooth muscle cells in airways and in the pulmonary vasculature. The hypothesis to be tested is that EC-SOD plays a critical role in regulating the activity of nitric oxide (NO.) in the lung. The possible mechanism for EC-SOD regulation of NO. activity involves scavenging O2- and thereby preventing the reaction of O2- with NO.. The distributions and physical relationships of nitric oxide synthase (the enzymatic source of NO.) and EC-SOD in pulmonary airways and in the pulmonary vasculature will be determined. Both in vitro and in vivo animal models will be used to demonstrate the role of EC-SOD in regulating airway and vascular tone in the lung. The Specific Aims are 1) Create tools for the study of EC-SOD in an animal model that will allow the biological function of EC-SOD to be explored, 2) Immunolocalize EC-SOD in airways and pulmonary vasculature, 3) Immunolocalize nitric oxide synthase in airways and pulmonary vasculature, 4) Study the mechanisms of airway bronchomotor tone regulation, and 5) Study the mechanisms of pulmonary vasculature tone regulation. These proposed studies are expected to demonstrate that EC-SOD plays a critical role in regulating both airway and vascular tone in the lung. By demonstrating the physiologic importance of this enzyme, we expect to identify new pharmacologic therapies for the treatment of diseases involving both airway hyperreactivity and pulmonary vascular hyperreactivity.