Lakari E, Pääkkö P, Pietarinen-Runtti P, Kinnula V L
Department of Internal Medicine, Oulu University Hospital, Oulu, Finland.
Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 1):615-21. doi: 10.1164/ajrccm.161.2.9904091.
Free radicals have been suggested to play an important role in the pathogenesis of interstitial lung diseases, the most important of which are chronic interstitial pneumonias such as usual interstitial pneumonia (UIP) and desquamative interstitial pneumonia (DIP) and granulomatous lung diseases such as sarcoidosis. Because manganese superoxide dismutase (MnSOD) and catalase are two important intracellular antioxidant enzymes that probably play a central role in lung defense, the localization and intensity of these two enzymes were assessed by immunohistochemistry in biopsies of UIP (n = 9), DIP (n = 11), pulmonary sarcoidosis (n = 14), and extrinsic allergic alveolitis (n = 6). The mRNA of these enzymes in selected samples of bronchoalveolar lavage was assessed by Northern blotting. Catalase, but not MnSOD, was constitutively expressed, especially in type II pneumocytes of the healthy lung of nonsmoking individuals. In contrast, manganese SOD immunoreactivity was markedly upregulated in all of the interstitial lung diseases investigated, whereas no increased expression of catalase could be detected in any case. Both enzymes were expressed, especially in type II pneumocytes and alveolar macrophages of DIP and UIP, in the well-preserved areas of the lung, in the acute fibromyxoid lesions of UIP, and in the granulomas of sarcoidosis and extrinsic allergic alveolitis. The simultaneous expression of MnSOD and catalase in the alveolar region suggests their protective role against the progression of lung disease.
自由基被认为在间质性肺疾病的发病机制中起重要作用,其中最重要的是慢性间质性肺炎,如寻常型间质性肺炎(UIP)和脱屑性间质性肺炎(DIP),以及肉芽肿性肺疾病,如结节病。由于锰超氧化物歧化酶(MnSOD)和过氧化氢酶是两种重要的细胞内抗氧化酶,可能在肺部防御中起核心作用,因此通过免疫组织化学方法对UIP(n = 9)、DIP(n = 11)、肺结节病(n = 14)和外源性过敏性肺泡炎(n = 6)的活检组织中这两种酶的定位和强度进行了评估。通过Northern印迹法对支气管肺泡灌洗所选样本中这些酶的mRNA进行了评估。过氧化氢酶而非MnSOD呈组成性表达,尤其是在不吸烟个体的健康肺脏的II型肺泡上皮细胞中。相反,在所有所研究的间质性肺疾病中,锰超氧化物歧化酶免疫反应性均显著上调,而在任何情况下均未检测到过氧化氢酶表达增加。这两种酶均有表达,尤其是在DIP和UIP的II型肺泡上皮细胞和肺泡巨噬细胞中、肺脏保存良好的区域、UIP的急性纤维黏液样病变中以及结节病和外源性过敏性肺泡炎的肉芽肿中。MnSOD和过氧化氢酶在肺泡区域的同时表达表明它们对肺部疾病进展具有保护作用。