Because antioxidant enzymes may have an important role in the oxidant resistance of inflammatory cells, we investigated the mRNA levels and specific activities of manganese and copper-zinc superoxide dismutases (Mn SOD and Cu,Zn SOD), catalase (Cat), and glutathione peroxidase, as well as the concentrations of glutathione (GSH) in human neutrophils, monocytes, monocyte-derived macrophages, and alveolar macrophages. Levels of GSH and glutathione peroxidase activity in monocytes were three times higher than in neutrophils, whereas the mRNA of Cat was 50-fold and its specific activity 4-fold higher in neutrophils. Although Mn SOD mRNA levels were higher in neutrophils, enzyme activities, as well as those of Cu,Zn SOD, were similar in all phagocytic cells. Neutrophils lost their viability, assessed by adenine nucleotide depletion, within 24 h ex vivo and more rapidly if GSH was depleted. However, neutrophils were the most resistant cell type to exogenous H(2)O(2). In conclusion, high Cat activity of neutrophils appears to explain their high resistance against exogenous H(2)O(2), whereas low GSH content and GSH-related enzymes seem to account for the poor survival of human neutrophils.

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.

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