Cannady Steven B, Batra Pete S, Leahy Rachel, Citardi Martin J, Janocha Allison, Ricci Kristin, Comhair Suzy A A, Bodine Melanie, Wang Zeneng, Hazen Stanley L, Erzurum Serpil C
Head and Neck Institute, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
J Allergy Clin Immunol. 2007 Dec;120(6):1346-53. doi: 10.1016/j.jaci.2007.07.067. Epub 2007 Nov 1.
Nasal polyposis is characterized by impaired regulation of nasal tissue growth and is associated with chronic inflammation, sinus infections, and low levels of nitric oxide (NO). Based on its critical role in mediating cell growth and antimicrobial function, decrease of NO levels has been implicated in the pathogenesis of nasal polyposis.
We sought to evaluate mechanisms for the low NO level in polyposis, including factors regulating NO synthase (NOS) expression and activity and NO consumptive processes in nasal epithelial cells and nasal lavage fluid.
Eighteen patients with nasal polyposis and 8 healthy control subjects were studied. Nasal brushings, nasal lavage fluid, and nasal biopsy specimens were collected and analyzed.
NO metabolite levels (nitrite and nitrate) in nasal lavage fluid from patients with polyps were less than those in control subjects, but activation of signal transduction and inducer of transcription 1, which regulates inducible NOS gene expression and protein expression, was present at higher levels in polyp than in healthy control tissue. Levels of arginine, methylarginine, and endogenous NOS inhibitors were similar between polyp and control tissue. In contrast, superoxide dismutase activity of polyp tissues was lower than that seen in control tissue and associated with increased nitrotyrosine, a biomarker of oxidant consumptive products of NO.
Taken together, these data suggest that the nasal polyp environment is characterized by abnormalities in NO metabolism that might predispose to altered regulation of tissue growth and infection.
Identification of NO metabolic abnormalities might lead to novel treatments for sinonasal polyposis targeted against the pathways identified within this study.
鼻息肉病的特征是鼻组织生长调节受损，并与慢性炎症、鼻窦感染和低水平一氧化氮（NO）相关。基于其在介导细胞生长和抗菌功能中的关键作用，NO水平降低被认为与鼻息肉病的发病机制有关。
我们试图评估息肉病中NO水平降低的机制，包括调节一氧化氮合酶（NOS）表达和活性的因素以及鼻上皮细胞和鼻灌洗液中的NO消耗过程。
对18例鼻息肉病患者和8名健康对照者进行研究。收集并分析鼻刷检物、鼻灌洗液和鼻活检标本。
息肉患者鼻灌洗液中的NO代谢物水平（亚硝酸盐和硝酸盐）低于对照者，但调节诱导型NOS基因表达和蛋白质表达的信号转导及转录激活因子1在息肉中的激活水平高于健康对照组织。息肉组织和对照组织中的精氨酸、甲基精氨酸和内源性NOS抑制剂水平相似。相反，息肉组织的超氧化物歧化酶活性低于对照组织，且与硝基酪氨酸增加有关，硝基酪氨酸是NO氧化消耗产物的生物标志物。
综上所述，这些数据表明鼻息肉环境的特征是NO代谢异常，这可能导致组织生长调节和感染的改变。
识别NO代谢异常可能会针对本研究中确定的途径开发出治疗鼻息肉病的新方法。
