Pathogenesis of emphysema. Assessment of basic science concepts through clinical investigation.
It is clear that alpha 1AT deficiency leads to early onset pulmonary emphysema. With the lead provided by the deficiency state, studies aimed at the linkage between alpha 1AT and its target enzyme, neutrophil elastase, have provided useful information about the pathogenesis of emphysema due to cigarette smoking. alpha 1AT represents the predominant antielastase of the lower respiratory tract. This observation implicates neutrophil elastase as the enzyme responsible for lung destruction, since affinity studies demonstrate that alpha 1ATs physiologically relevant function is the inhibition of neutrophil elastase. However, because of the inexorably slow nature of the emphysema process, demonstration of the protease-antiprotease imbalance in the lungs of smokers has been difficult. Studies using sensitive assays for alpha 1AT function and for neutrophil elastase's presence have added new support for the protease-antiprotease theory, and evaluation of related disorders such as the adult respiratory distress syndrome and cystic fibrosis have provided corraborative evidence. Finally, studies that have indicated that the major site of the protease-antiprotease imbalance is the microenvironment of protease-producing cells offer a new direction for future research into the pathogenesis of emphysema.
Wewers
M
M
Ohio State University, Columbus.
D001992:Bronchoalveolar Lavage Fluid / Q000032:analysis; D003550:Cystic Fibrosis / Q000201:enzymology; D006801:Humans; D008168:Lung / Q000201:enzymology; D009504:Neutrophils / Q000201:enzymology; D010196:Pancreatic Elastase / Q000378:metabolism; D011656:Pulmonary Emphysema / Q000201:enzymology / Q000209:etiology*; D012128:Respiratory Distress Syndrome / Q000201:enzymology / Q000209:etiology; D012907:Smoking; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D019896:alpha 1-Antitrypsin Deficiency
D000515:alpha 1-Antitrypsin; D010196:Pancreatic Elastase