Manganese Superoxide Dismutase and Catalase Are Coordinately Expressed in the Alveolar Region in Chronic Interstitial Pneumonias and Granulomatous Diseases of the Lung

Abstract

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.

Manganese superoxide dismutase is increased in the airways of smokers' lungs

“…Only a few studies have investigated MnSOD in human lung diseases. MnSOD is elevated in the inflammatory phases of interstitial lung diseases [14,16]. In contrast, the RNA levels of MnSOD appear to be very similar in the central airways of nonsmokers and smokers [20].…”

“…Cell-specific expression of MnSOD has been detected in the human lung [14], but its immunoreactivity has not been previously compared at various levels of the airways. Consistent with the previous findings, MnSOD was expressed in central bronchial epithelium, as well as in alveolar macrophages, but the expression was much weaker in peripheral airways than in the bronchial epithelium of large airways.…”

“…For immunohistochemical analysis, 4-mm sections were cut. Immunohistochemistry was conducted with aminoethyl carbazole (Zymed Laboratories Inc., San Francisco, CA, USA) as described by LAKARI et al [14]. The primary polyclonal antibodies for CuZnSOD, MnSOD, ECSOD [15][16][17] and 4-HNE (Calbiochem Co., La Jolla, CA, USA) with dilutions of 1:200 for CuZnSOD, 1:1,000 for MnSOD, 1:200 for ECSOD and 1:250 for 4-HNE were used.…”

“…A potential mechanism contributing to cigarette smoke-related lung diseases is oxidant stress that overwhelms the primary antioxidant defence of the lung [1][2][3][4]. One puff containsy10 14 -10 16 of free radicals [4] and the airways of COPD patients contain large amounts of neutrophils, potent generators of free radicals. Cigarette smoke also activates redox-sensitive transcription factors, such as nuclear factor-kB in COPD [5], which has been shown to regulate the genes of several antioxidant enzymes and related proteins in the lung [6,7].…”

Distribution of Antioxidant Enzymes in Developing Human Lung, Respiratory Distress Syndrome, and Bronchopulmonary Dysplasia

“…Our study with the AEC method, which is highly sensitive, confirmed the recent results with the diamino benzidine (DAB) method (Asikainen et al 2001) on the expression of MnSOD already during the 17th gestational week in human bronchial epithelium, developing alveolar epithelium, and alveolar macrophages. In healthy adult human lung, MnSOD is weakly expressed, especially in type II pneumocytes, alveolar macrophages, and bronchiolar epithelial cells (Kinnula et al 1994;Coursin et al 1996;Lakari et al 1998Lakari et al ,2000.…”