Characteristic elevation of matrix metalloproteinase activity in idiopathic interstitial pneumonias

Am J Respir Crit Care Med. 2000 Nov;162(5):1949-56. doi: 10.1164/ajrccm.162.5.9906096.


Destruction of subepithelial basement membrane is a key event in the pathogenesis of idiopathic pulmonary fibrosis (IPF). To evaluate the role of matrix metalloproteinases (MMPs) in parenchymal remodeling in idiopathic interstitial pneumonia (IIP), we studied MMP-2 and -9 activity, in bronchoalveolar lavage fluid (BALF) by zymography and the expression of MMP-2 and -9 and TIMP-2 in lung tissue by immunohistochemistry. BALF and lung tissues were collected from 26 patients with usual interstitial pneumonia (IPF-UIP), 11 with nonspecific interstitial pneumonia (NSIP), and 6 with bronchiolitis obliterans organizing pneumonia (BOOP). IPF-UIP cases showed predominant expression of MMP-9, whereas NSIP and BOOP cases showed predominant MMP-2 expression in BALF and in tissues. In BALF samples from rapidly progressive IPF-UIP cases, neutrophil-derived MMP-9 activity, as well as MMP-9 active form were characteristically detected. Furthermore, the MMP-9 activity correlated significantly with an increase of neutrophils in BALF, whereas the MMP-2 activity associated with NSIP and BOOP correlated with an increase of lymphocytes. These results indicate that MMP-9 in IPF-UIP and MMP-2 in NSIP and BOOP may contribute to pulmonary structural remodeling through type IV collagenolytic activity. The characteristic contributions of matrix-degrading proteins may relate to the distinct prognostic features of these diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cryptogenic Organizing Pneumonia / metabolism
  • Female
  • Humans
  • Immunohistochemistry
  • Lung / enzymology*
  • Lung Diseases, Interstitial / enzymology*
  • Male
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Middle Aged
  • Tissue Inhibitor of Metalloproteinase-2 / metabolism


  • Tissue Inhibitor of Metalloproteinase-2
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9