Potentiative effects of neutral proteinases in an inflamed lung: relationship of neutrophil procollagenase (proMMP-8) to plasmin, cathepsin G and tryptase in bronchiectasis in vivo

Eur Respir J. 1997 Dec;10(12):2788-93. doi: 10.1183/09031936.97.10122788.

Abstract

We attempted to study the possible relationships between neutrophil-type procollagenase/pro-matrix metalloproteinase (MMP-8) and the serine proteinases plasmin, cathepsin G and tryptase in bronchiectasis. The presence of the plasmin/plasminogen system and plasmin-, cathepsin G- and tryptase-like activities were compared to the activity of endogenously activated MMP-8 in bronchoalveolar lavage (BAL) fluid in 38 bronchiectasis patients and in 14 healthy controls by means of immunohistochemistry, Western-blot and substrate-based functional assays. In contrast to cathepsin G- and tryptase-like activities, the plasmin/plasminogen activator system in BAL fluid was observed to have a relatively weak activation stage and no correlation with disease severity. Neither plasmin-like activities nor concentrations of plasminogen activators from the bronchiectatic patients differed significantly from the values of healthy controls. Immunolocation of plasminogen activator inhibitor-1 showed a marked, but not significant, increase in bronchiectatic lung as compared to controls. In contrast to cathepsin G- and tryptase-like activities, with their strong and significant correlation with endogenously activated collagenase (r=0.9; p=0.0001; and r=0.6; p=0.03, respectively), no correlations were observed between plasmin-like and endogenously activated collagenase (r=0.3; p=0.2) in bronchiectasis. These findings suggest that cathepsin G- and tryptase-like activities may act as potent pro-matrix metalloproteinase-8 activators in patients with bronchiectasis, whereas the plasminogen activator/plasmin cascade was shown to be down-regulated.

Publication types

  • Clinical Trial
  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Analysis of Variance
  • Biopsy
  • Blotting, Western
  • Bronchiectasis / diagnosis
  • Bronchiectasis / enzymology*
  • Bronchiectasis / pathology
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cathepsin G
  • Cathepsins / analysis*
  • Chymases
  • Collagenases / analysis*
  • Down-Regulation
  • Female
  • Fibrinolysin / analysis*
  • Humans
  • Immunohistochemistry
  • In Vitro Techniques
  • Inflammation Mediators / analysis*
  • Lung / enzymology*
  • Lung / pathology
  • Male
  • Matrix Metalloproteinase 8
  • Neutrophil Activation
  • Serine Endopeptidases / analysis*
  • Tryptases

Substances

  • Inflammation Mediators
  • Cathepsins
  • Serine Endopeptidases
  • chymase 2
  • CTSG protein, human
  • Cathepsin G
  • Chymases
  • Tryptases
  • Fibrinolysin
  • Collagenases
  • Matrix Metalloproteinase 8