Emphysema

Emphysema is a chronic lung disease. It is often caused by exposure to toxic chemicals or long-term exposure to tobacco smoke.

Pathogenesis

While A1AD provides some insight into the pathogenesis of the disease, hereditary A1AT deficiency only accounts for a small proportion of the disease. Studies for the better part of the past century have focused primarily upon the putative role of leukocyte elastase (also neutrophil elastase), a serine protease found in neutrophils, as a primary contributor to the connective tissue damage seen in the disease. This hypothesis, a result of the observation that NE is the primary substrate for A1AT, and A1AT is the primary inhibitor of NE, together have been known as the "protease-antiprotease" theory, implicating neutrophils as an important mediator of the disease. However, more recent studies have brought into light the possibility that one of the many other numerous proteases, especially matrix metalloproteases might be equally or more relevant than NE in the development of non-hereditary emphysema.

Related Topics:
Leukocyte - Elastase - Protease

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The better part of the past few decades of research into the pathogenesis of emphysema involved animal experiments where various proteases were instilled into the trachea of various species of animals. Needless to say, these poor animals developed connective tissue damage, which was taken as support for the protease-antiprotease theory. However, just because these substances can destroy connective tissue in the lung, as anyone would be able to predict, doesn't establish causality. More recent experiments have focused on more technologically advanced, but equally archaic theoretical approaches, using genetic manipulation. Perhaps the most interesting development with respect to our understanding of the disease involves the production of protease 'knock-out' animals, which are genetically deficient in one or more proteases, and assessing whether they would be less prone to the development of the disease. However, the exact pathogenesis of this disease is unlikely to be unravelled in great detail in the near future.

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