Watkins D N, Lewis R H, Basclain K A, Fisher P H, Peroni D J, Garlepp M J, Thompson P J
The University Department of Medicine, Queen Elizabeth II Medical Centre, Nedlands, Western Australia.
Clin Exp Allergy. 1998 Feb;28(2):211-9. doi: 10.1046/j.1365-2222.1998.00215.x.
The pathogenesis of nasal polyp disease is poorly understood. Recent evidence has suggested that nitric oxide (NO), an endogenous soluble gas vasodilator and inflammatory mediator, may be synthesised within the nasal cavity. Three nitric oxide synthase isoforms have been identified in humans, with the inducible isoform (iNOS) generally expressed in the setting of inflammation.
The aim of this study was to detect and localize iNOS expression in nasal polyp tissue, and compare these findings with normal nasal turbinate tissue.
We examined the expression and localisation of inducible nitric oxide synthase (iNOS) in human nasal airway specimens from patients undergoing elective nasal turbinectomy (n = 5) or nasal polypectomy (n = 5). iNOS mRNA expression was determined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) followed by Southern blot analysis and localised by in situ hybridization. Densitometric data were analysed using Student's unpaired t-test. Adjacent sections were also examined for iNOS protein expression by immunohistochemistry.
Semi-quantitative RT-PCR/Southern analysis of RNA obtained from the 10 surgical specimens demonstrated that iNOS mRNA expression was significantly increased in the five nasal polyps (P < 0.05). In situ hybridization studies revealed strong iNOS mRNA signal localized to the respiratory epithelium of nasal polyps, but not nasal turbinates. This pattern was confirmed by immunohistochemistry. Localization to inflammatory cells or other subepithelial structures was not seen.
We conclude that iNOS expression is upregulated in nasal polyp disease, and is localized to the polyp epithelial layer. These data reinforce the concept that the epithelial layer may be important in the pathogenesis of nasal disease, and suggest a potential role for NO in the formation of nasal polyps.
鼻息肉病的发病机制尚不清楚。最近有证据表明，一氧化氮（NO）作为一种内源性可溶性气体血管舒张剂和炎症介质，可能在鼻腔内合成。已在人类中鉴定出三种一氧化氮合酶亚型，其中诱导型亚型（iNOS）通常在炎症环境中表达。
本研究旨在检测并定位鼻息肉组织中iNOS的表达，并将这些结果与正常鼻甲组织进行比较。
我们检测了接受选择性鼻甲切除术（n = 5）或鼻息肉切除术（n = 5）患者的人类鼻气道标本中诱导型一氧化氮合酶（iNOS）的表达和定位。通过半定量逆转录聚合酶链反应（RT-PCR），随后进行Southern印迹分析来确定iNOS mRNA表达，并通过原位杂交进行定位。使用学生未配对t检验分析光密度数据。相邻切片也通过免疫组织化学检查iNOS蛋白表达。
对从10个手术标本中获得的RNA进行半定量RT-PCR/Southern分析表明，5个鼻息肉中iNOS mRNA表达显著增加（P < 0.05）。原位杂交研究显示，强烈的iNOS mRNA信号定位于鼻息肉的呼吸上皮，但不在鼻甲中。免疫组织化学证实了这种模式。未观察到定位于炎症细胞或其他上皮下结构。
我们得出结论，在鼻息肉病中iNOS表达上调，且定位于息肉上皮层。这些数据强化了上皮层在鼻病发病机制中可能很重要的概念，并提示NO在鼻息肉形成中可能发挥作用。
