Two decades of research in the pathogenesis of emphysema.
Alpha 1 antiprotease is the major antiprotease (or antielastase) in the lungs. Neutrophils are the major source of elastase. Elastases damage interstitial elastic fibers giving rise to elastase-antielastase imbalance and to emphysema. Lung volume and volume-pressure (VP) curve is shifted up and to the left in elastase treated hamsters compared to the controls; quasi-static compliance increases from 0.52 ml/cm to 0.92 ml/cm in the elastase treated animals. The histologic, stereologic and physiologic data of hamster's emphysema are all similar to the changes observed in human emphysema. Cigarette smoke is rich in oxidants inactivating alpha 1 antiproteases. There is also a decrease in the level of alpha 1 antiproteases in lavage fluid of smokers. An intensive search is now underway for synthetic antielastases which might be safely given to persons who are at risk of developing emphysema.
D000590:Amino Acid Chloromethyl Ketones / Q000627:therapeutic use; D000818:Animals; D001991:Bronchitis / Q000150:complications; D006224:Cricetinae; D003613:Danazol / Q000627:therapeutic use; D004285:Dogs; D004549:Elastin / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000201:enzymology; D008264:Macrophages / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011650:Pulmonary Alveoli / Q000166:cytology; D011656:Pulmonary Emphysema / Q000188:drug therapy / Q000209:etiology*; D051381:Rats; D012907:Smoking; D000515:alpha 1-Antitrypsin / Q000502:physiology
D000590:Amino Acid Chloromethyl Ketones; D000515:alpha 1-Antitrypsin; D004549:Elastin; D010196:Pancreatic Elastase; D003613:Danazol