Morrissey Brian M, Schilling Kevin, Weil John V, Silkoff Philip E, Rodman David M
Division of Pulmonary and Critical Care Medicine, University of California, Davis and Department of Pulmonary Sciences and Critical Care Medicine, Sacramento, CA 95817, USA.
Arch Biochem Biophys. 2002 Oct 1;406(1):33-9. doi: 10.1016/s0003-9861(02)00427-7.
Cystic fibrosis (CF), characterized by chronic airway infection and inflammation, ultimately leads to respiratory failure. Exhaled nitric oxide (NO), elevated in most inflammatory airway diseases, is decreased in CF, suggesting either decreased production or accelerated metabolism of NO. The present studies performed on two groups of CF patients provide further support for a disordered NO airway metabolism in CF respiratory tract disease. Despite confirmation of subnormal NOS2 in the CF airway epithelium, alternative isoforms NOS1 and NOS3 were present, and inflammatory cells in the CF airway expressed abundant NOS2. Increased immunohistochemical staining for nitrotyrosine was demonstrated in lung tissues from patients with CF as compared to control. To our knowledge, this is the first report localizing nitrotyrosine in diseased CF lung tissue. While the relative NOS2 deficiency in CF respiratory tract epithelium may contribute to the lower expired NO levels, these results suggest that increased metabolism of NO is also present in advanced CF lung disease. The significance of altered NO metabolism and protein nitration in CF remains to be fully elucidated.
囊性纤维化（CF）以慢性气道感染和炎症为特征，最终会导致呼吸衰竭。呼出一氧化氮（NO）在大多数炎症性气道疾病中会升高，但在CF患者中却降低，这表明NO的生成减少或代谢加快。目前对两组CF患者进行的研究进一步支持了CF呼吸道疾病中NO气道代谢紊乱的观点。尽管已证实CF气道上皮中的一氧化氮合酶2（NOS2）低于正常水平，但替代亚型一氧化氮合酶1（NOS1）和一氧化氮合酶3（NOS3）仍存在，并且CF气道中的炎症细胞表达了丰富的NOS2。与对照组相比，CF患者肺组织中硝基酪氨酸的免疫组化染色增加。据我们所知，这是首次在患病的CF肺组织中定位硝基酪氨酸的报告。虽然CF呼吸道上皮中相对缺乏NOS2可能导致呼出NO水平降低，但这些结果表明，在晚期CF肺病中也存在NO代谢增加的情况。CF中NO代谢改变和蛋白质硝化的意义仍有待充分阐明。
