Proteinase-antiproteinase imbalance in the pathogenesis of emphysema: The role of metalloproteinases in lung damage

Abstract

Pulmonary emphysema refers to a lung disorder characterized by a diffuse destruction of the alveolar walls resulting in enlargement of the distal airspaces. The disease is usually a chronic, progressive, and disabling disorder. The concept of proteinase/antiproteinase imbalance evolved from the identification of patients with alpha 1-antytripsin deficiency, and from the development of experimental emphysematous lesions using different enzymes. For a long time, this concept was seen as an elastase/antielastase imbalance, with the consequent degradation of elastin. Recent evidence, however, suggests that an intricate process of pulmonary remodeling occurs during the development of emphysema, where a complex network of serine proteases and metalloproteinases capable of degrading different extracellular matrix molecules, primarily, but not exclusively fibrillar collagens and elastin, are implicated in the pathogenesis of this disease.