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

Sepper R, Konttinen YT, Buo L, et al. 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. EUROPEAN RESPIRATORY JOURNAL. 1997;10(12):2788-2793.We attempted to study the possible relationships between neutrophiltype procollagenase/pro-matrix metalloproteinase (MMP-8) and the serine proteinases plasmin, cathepsin G and tryptase in bronchiectasis. The presence of the plasmin/piasminogen 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 substratebased 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 health. 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,,vith 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 bronrhiectasis, whereas the plasminogen activator/plasmin cascade was shown to be down-regulated