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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.

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.
AuthorsR Sepper, Y T Konttinen, L Buø, K K Eklund, A Lauhio, T Sorsa, H Tschesche, A O Aasen, H Sillastu
JournalThe European respiratory journal (Eur Respir J) Vol. 10 Issue 12 Pg. 2788-93 (Dec 1997) ISSN: 0903-1936 [Print] England
PMID9493662 (Publication Type: Clinical Trial, Controlled Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Inflammation Mediators
  • Cathepsins
  • Serine Endopeptidases
  • chymase 2
  • CTSG protein, human
  • Cathepsin G
  • Chymases
  • Tryptases
  • Fibrinolysin
  • Collagenases
  • Matrix Metalloproteinase 8
Topics
  • Adolescent
  • Adult
  • Analysis of Variance
  • Biopsy
  • Blotting, Western
  • Bronchiectasis (diagnosis, enzymology, 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, pathology)
  • Male
  • Matrix Metalloproteinase 8
  • Neutrophil Activation
  • Serine Endopeptidases (analysis)
  • Tryptases

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