title: 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.
authors.affiliation: Dept of Anatomy, Institute of Biomedicine, University of Helsinki, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Sepper
authors.forename: Y T
authors.initials: YT
authors.lastname: Konttinen
authors.forename: L
authors.initials: L
authors.lastname: Buø
authors.forename: K K
authors.initials: KK
authors.lastname: Eklund
authors.forename: A
authors.initials: A
authors.lastname: Lauhio
authors.forename: T
authors.initials: T
authors.lastname: Sorsa
authors.forename: H
authors.initials: H
authors.lastname: Tschesche
authors.forename: A O
authors.initials: AO
authors.lastname: Aasen
authors.forename: H
authors.initials: H
authors.lastname: Sillastu
mesh_terms: D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001706:Biopsy; D015153:Blotting, Western; D001987:Bronchiectasis / Q000175:diagnosis / Q000201:enzymology* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D056649:Cathepsin G; D002403:Cathepsins / Q000032:analysis*; D053818:Chymases; D017364:Collagenases / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D005341:Fibrinolysin / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000032:analysis*; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D008297:Male; D020784:Matrix Metalloproteinase 8; D018375:Neutrophil Activation; D012697:Serine Endopeptidases / Q000032:analysis*; D053802:Tryptases
chemical_list: D018836:Inflammation Mediators; D002403:Cathepsins; D012697:Serine Endopeptidases; C083294:chymase 2; C534094:CTSG protein, human; D056649:Cathepsin G; D053818:Chymases; D053802:Tryptases; D005341:Fibrinolysin; D017364:Collagenases; D020784:Matrix Metalloproteinase 8