MANGANESE SUPEROXIDE-DISMUTASE, BUT NOT CUZN SUPEROXIDE-DISMUTASE, ISHIGHLY EXPRESSED IN THE GRANULOMAS OF PULMONARY SARCOIDOSIS AND EXTRINSIC ALLERGIC ALVEOLITIS

The role of antioxidant defense mechanisms in the pathogenesis of gran ulomatous human lung diseases remains open to investigation. In this s tudy we investigated the immunoreactivity of two important superoxide radical scavenging intracellular antioxidant enzymes, manganese supero xide dismutase (MnSOD) and copperzinc superoxide dismutase (CuZnSOD), in pulmonary sarcoidosis and extrinsic allergic alveolitis. In histolo gically normal lung MnSOD was variable but mostly positive in the cell s of bronchial epithelium, alveolar epithelium especially in type II p neumocytes, and alveolar macrophages. Copperzinc SOD showed positive i mmunoreactivity most markedly in the bronchial epithelium. The biopsie s of 22 patients with pulmonary sarcoidosis and 10 with extrinsic alle rgic alveolitis indicated that MnSOD was highly stained in the granulo mas of both diseases, with 60 to 100% of the granulomas showing intens ive immunoreactivity. Western blots conducted on the cell samples of b ronchoalveolar lavage (BAL) fluid revealed significantly higher amount s of MnSOD in sarcoidosis and extrinsic allergic alveolitis than in th e controls. Immunohistochemistry on the cells obtained from BAL fluid showed positive immunoreactivity of MnSOD in the macrophages but not i n the lymphocytes. In contrast, copperzinc SOD was not induced in eith er of these diseases. We conclude that MnSOD is highly expressed in th e granulomas of pulmonary sarcoidosis and extrinsic allergic alveoliti s, and variable but mostly positive in alveolar macrophages, possibly owing to cytokine mediated induction during the granuloma formation.