Inducible Nitric Oxide Synthase Was Generally Expressed in Inflammatory, Infectious, and Malignant Lung Diseases

誘發性一氧化氮合成酶的表現廣泛增加於肺臟疾病

林啟嵐(Chii-Lan Lin) ； 楊美貞(Mei-Chen Yang) ； 黃崇仁(Chong-Ren Huang) ； 余志騰(Chih-Teng Yu) ； 王圳華(Chun-Hua Wang) ； 陳澤卿(Tse-Ching Chen) ； 郭漢彬(Han-Pin Kuo) ； 劉劍英(Chien-Ying Liu)

《胸腔醫學》 18卷4期 (2003/08) Pp. 301-314

摘要

一氧化氮合成酶催化產生一氧化氮媒介了無數的生理、發炎和感染性反應。為了進一步釐清一氧化氮在肺臟發炎、感染和腫瘤病變中的複雜角色，我們利用免疫組織化學染色方法，探索組成性（constitutional）及誘發性（inducible）一氧化氮合成酶在這些組織的表現。我們分析一些人類呼吸道及肺實質疾病，包括慢性阻塞性肺病、支氣管擴張症、慢性肺炎、肺膿瘍、病毒性肺炎、黴菌性肺炎、肺結核和原發性肺癌。抗組成性一氧化氮合成酶（anti-cNOS）之免疫組織染色確定組成性一氧化氮合成?抗原存在於神經、內皮細胞和一些肺泡巨噬細胞。抗誘發性一氧化氮合成酶（anti-iNOS）免疫組織染色顯示肺泡巨噬細胞、組織巨噬細胞、內皮細胞被強烈標記。氣管上皮細胞、腺細胞、血管平滑肌則呈中度標記。誘發性一氧化氮合成酶染色也呈現於支氣管淋巴組織、組織血管內邊緣及組織中的多核性白血球、間皮細胞、巨細胞病毒感染的細胞、類上皮細胞、以及軟骨細胞。我們也確定誘發性一氧化氮合成酶在肺臟扁平細胞癌、腺癌和小細胞癌的表現。周邊血管循環中與組織血管內邊緣或血管滲出的多核性白血球之誘發性一氧化氮合成酶表現不相同，而且循環中與組織的淋巴球、單核球或巨噬細胞之誘發性一氧化氮合成酶表現也不相同。我們的實驗結果顯示，不論是發炎、感染或腫瘤性肺病變，許多肺臟的組成組織均表現出誘發性一氧化氮合成酶之活性。本研究進一步拓展了吾人對一氧化氮在肺臟免疫防禦機轉及腫瘤生成病理機制的認知和了解。

關鍵字

一氧化碳合成酶 ； 慢性阻塞性肺病 ； 肺炎 ； 肺癌

並列摘要

Nitric oxide synthase (NOS) produces nitric oxide (NO), a mediator of importance in numerous physiologic, inflammatory, and infectious processes in the lung. For further clarification of the complex role of NO in the pathogenesis of infectious, inflammatory, and malignant lung diseases, we explored constitutive NOS (cNOS) and inducible NOS (iNOS) localization using immunohistochemistry. We analyzed human airway and parenchyma specimens obtained from patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, chronic pneumonia, lung abscess, viral pneumonia (cytomegalovirus, CMV), fungal pneumonia (aspergillosis), pulmonary tuberculosis, and primary lung malignancy. Immunostaining with anti-c-NOS identified cNOS antigen in the nerve, endothelium and some alveolar macrophages. Immunostaining with anti-iNOS showed strong labeling of the alveolar macrophages, tissue-associated macrophages, and endothelium; and moderate labeling of the bronchial epithelium, glandular cells, and smooth muscle of the vascular wall. iNOS staining was also detected in bronchial-associated lymphoid tissue (BALT), marginated and tissue polymorphonuclear leukocytes, mesothelial cells, CMV infected cells, and epithelioid cells around the tubercles and chondrocytes. Furthermore, we also identified iNOS expression in squamous cell and small cell carcinomas, and in adenocarcinoma. The circulatory and the marginated and extravasated polymorphonuclear leukocytes have different expressions of iNOS activity. The expressions of iNOS between the circulatory and the tissue-associated lymphocytes and monocytes/macrophages are also quite different. Our results indicate that numerous distinct constitutive compartments within the lungs of patients with inflammatory, infectious, or malignant diseases contain iNOS activity. This study further extends our knowledge of the role of NO in the defense mechanisms and the oncogenetic processes of the lung, and may provide new insights into the pathophysiology of these lung diseases.

並列關鍵字

nitric oxide synthase ； chronic obstructive pulmonary disease ； pneumonia ； lung cancer