The role of oxidative processes in emphysema.
Elastase/elastase inhibitor imbalance in the lung has been implicated in the pathogenesis of pulmonary emphysema. In light of this, it may be significant that the activity of two major elastase inhibitors, alpha 1-proteinase inhibitor (alpha 1-antitrypsin, alpha 1Pi) and bronchial mucous proteinase inhibitor, can be decreased by oxidizing agents. The effect can be observed with ozone, substances present in cigarette smoke, and oxygen metabolites generated by lung macrophages as well as peroxidative systems released by other phagocytic cells. Thus alpha 1Pi recovered from lung washings of cigarette smokers has only half the predicted normal activity per mg inhibitor and contains 4 moles of methionine sulfoxide (oxidized methionine) per mole of inactive inhibitor. By contrast, alpha 1Pi purified from nonsmokers' lung washings is fully active and contains only native methionine. At the same time, lung washes from some smokers show significantly greater hydrolytic activity against a specific synthetic elastase substrate than do lung washes of nonsmokers. These findings suggest that some smokers may develop an acquired imbalance between elastase and elastase inhibitor in their lungs, favoring activity of the enzyme. In addition to the potential effect of cigarette smoking on lung elastase/elastase inhibitor balance, smoking also may interfere with elastin repair mechanisms. Specifically, acidic water-soluble gas phase components of cigarette smoke prevent synthesis of desmosine cross-links during elastinogenesis in vitro. This report will attempt to correlate the foregoing information on biochemical changes in the lung induced by cigarette smoking with the development of emphysema in the smoker.
D004357:Drug Synergism; D004789:Enzyme Activation; D005609:Free Radicals; D006801:Humans; D008168:Lung / Q000166:cytology / Q000201:enzymology; D008264:Macrophages / Q000378:metabolism; D008715:Methionine / Q000378:metabolism / Q000494:pharmacology; D009504:Neutrophils / Q000201:enzymology; D010084:Oxidation-Reduction; D010196:Pancreatic Elastase / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism / Q000494:pharmacology; D010586:Phagocytes / Q000378:metabolism; D010947:Plants, Toxic; D011480:Protease Inhibitors / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000503:physiopathology*; D012906:Smoke; D014026:Nicotiana; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D005609:Free Radicals; D010545:Peroxides; D011480:Protease Inhibitors; D012906:Smoke; D000515:alpha 1-Antitrypsin; D008715:Methionine; D010196:Pancreatic Elastase