| Expression of oxidant and antioxidant enzymes in human lung and interstitial lung diseases | ||
|---|---|---|
| Prev | Chapter 6. Discussion | Next |
We found for the first time that MnSOD is highly expressed in the granulomas of sarcoidosis and extrinsic allergic alveolitis in human lung. This finding was constant and repeatable not only in the granulomas, but also in the lymph nodes of six patients with sarcoidosis. High MnSOD immunoreactivity was also detected in alveolar macrophages and type II pneumocytes both in the patients with sarcoidosis and extrinsic allergic alveolitis. Both of these cells are also more resistant to exogenous oxidants than alveolar type I cells or endothelial cells (Crapo et al. 1980). Western blotting revealed significantly higher level of MnSOD in the BAL cell samples in sarcoidosis and extrinsic allergic alveolitis than in the controls, and immunohistochemistry indicated that MnSOD was expressed in alveolar macrophages, but not in the lymphocytes. Since the percentage of macrophages in the BAL samples of healthy controls is higher than in granulomatous diseases associated with relative lymphocytosis, the results of the Western blotting underestimate the real expression of MnSOD in the macrophages of these diseases. The pathogenesis of hypersensitivity granulomatous diseases is still partially unclear, but it can be hypothesized that free radicals may have a central contributing role in these diseases. Granuloma formation involves several cytokines and lymphokines, such as TNF-α, 1L-1 and IL-6, all of which can cause MnSOD induction (Wong & Goeddel 1988, Visner et al. 1990, Warner et al. 1991, Harris et al. 1991). Since these granulomatous diseases are usually benign and lung architecture is well preserved, the enhanced expression of MnSOD may play an important role in protection of the lung during macrophage activation and granuloma formation. It is known that MnSOD is localized in alveolar macrophages, and against this background, it is natural that MnSOD is also expressed in granulomas, which originate from monocyte lineages, i.e. macrophages.