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

Histol Histopathol. 1999 Jan;14(1):227-33. doi: 10.14670/HH-14.227.


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.

Publication types

  • Review

MeSH terms

  • Animals
  • Endopeptidases / physiology
  • Humans
  • Lung / pathology*
  • Lung Injury
  • Metalloendopeptidases / physiology*
  • Pulmonary Emphysema / pathology*
  • alpha 1-Antitrypsin / physiology*


  • alpha 1-Antitrypsin
  • Endopeptidases
  • Metalloendopeptidases