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

We attempted to study the possible relationships between neutrophiltyp e procollagenase/pro-matrix metalloproteinase (MMP-8) and the serine p roteinases plasmin, cathepsin G and tryptase in bronchiectasis. The pr esence of the plasmin/piasminogen system and plasmin-, cathepsin G-and tryptase-like activities were compared to the activity of endogenousl y activated MMP-8 in bronchoalveolar lavage (BAL) fluid in 38 bronchie ctasis patients and in 14 healthy controls by means of immunohistochem istry, Western-blot and substratebased functional assays, In contrast to cathepsin G-and tryptase-like activities, the plasmin/plasminogen a ctivator system in BAL fluid was observed to have a relatively weak ac tivation stage and no correlation with disease severity, Neither plasm in-like activities nor concentrations of plasminogen activators from t he bronchiectatic patients differed significantly from the values of h ealth. controls, Immunolocation of plasminogen activator inhibitor-1 s howed a marked, but not significant, increase in bronchiectatic lung a s compared to controls, In contrast to cathepsin G-and tryptase-like a ctivities,,vith their strong and significant correlation with endogeno usly activated collagenase (r=0.9; p=0.0001; and r=0.6; p=0.03, respec tively), no correlations were observed between plasmin-like and endoge nously activated collagenase(r=0.3; p=0.2) in bronchiectasis. These fi ndings suggest that cathepsin G-and tryptase-like activities may act a s potent pro-matrix metalloproteinase-8 activators in patients with br onrhiectasis, whereas the plasminogen activator/plasmin cascade was sh own to be down-regulated.