Oxidants, antioxidants and the pathogenesis of emphysema.
alpha 1-Antitrypsin Deficiency
Emphysema is a chronic pulmonary disorder characterized by a permanent enlargement of the air spaces distal to the terminal bronchioles consequent to destruction of the alveolar walls, including the epithelial and endothelial cells and the connective tissue matrix. There is increasing evidence that an imbalance of oxidants and antioxidants in the lower respiratory tract contributes to this process. Oxidants such as O2-., H2O2, OH, OCl- are generated in the lower respiratory tract as a result of normal biochemical processes, activation of inflammatory cells and inhaled toxic gases. Under normal circumstances, the parenchymal cells are protected by intracellular antioxidants and membrane radical scavengers. In addition, the fluid lining the epithelial surface contains a catalase-like antioxidant that protects the epithelial cells from oxidants. If the oxidant burden overcomes these defenses, the parenchymal cells may be injured, the connective tissue matrix may be partially degraded, the antiprotease screen that protects the lower respiratory tract from attack by neutrophil elastase may be rendered impotent. The alveolar wall then becomes highly vulnerable to elastolytic attack, with a complete destruction of the interstitial connective tissue matrix. In this regard, it is reasonable to hypothesize that reestablishment of the oxidant-antioxidant balance in favor of the antioxidants would be useful as a therapeutic strategy to suppress the emphysematous process.