Pathogenic Mechanisms in Emphysema: From Protease Anti–Protease Imbalance to Apoptosis

In 1963, Laurel and Erickson reported their discovery of severe ┙1-antitrypsin (AAT) deficiency and its association with emphysema (Laurell & Erickson, 1963). Soon after, Gross and coworkers reported that emphysema was induced in rats by the intratracheal instillation of a proteolytic enzyme (Gross et al.,1965). These findings led to the proteolytic hypothesis of emphysema (Janoff, 1985) which considers that emphysema develops as a result of the smoking-induced release of proteolytic enzymes from the increased number of neutrophils and macrophages in the lung. Proteolysis of lung connective tissue (more specifically elastin) occurs because the released proteases may not be fully inhibited by antiproteases, resulting in emphysema. However, although proteolysis may have a significant pathogenic role particularly in AAT deficiency, other pathogenic mechanism, such as oxidants either from inhaled smoke or from inflammatory cells, inflammation, T lymphocyte cell mediated immunity, and apoptosis have a significant pathogenic role (MacNee, a2005).