Association of trypsin-2 with activation of gelatinase B and collagenase-2 in human bronchoalveolar lavage fluid in vivo.
BACKGROUND
Tissue injury mediated by matrix metalloproteinases (MMPs) is a hallmark of inflammatory lung diseases. Latent secreted proMMPs must be activated to be catalytically competent.


OBJECTIVE
Our aim was to analyse an involvement of the trypsin-2, trypsin-2-alpha1-proteinase inhibitor (PI) complex and tumour-associated trypsin inhibitor (TATI) in the in vivo activation of proMMP-8, -9 and -2.


METHODS
Concentrations of trypsin-2, trypsin-2-alpha1-PI complex and TATI in bronchoalveolar lavage fluid (BALF) were analysed by immunofluorometry. Molecular forms and expression of trypsin-2 and trypsin-2-alpha1-PI complex were identified by Western immunoblot and immunocytochemistry. Gelatinolytic and collagenolytic activities were measured by substrate-based activity assays.


RESULTS
BALFs from 16 of 43 patients and BALFs from five of 15 healthy controls contained trypsin-2-alpha1-PI complex. TATI was found in all healthy control BALFs (median 0.12 microg/L, range 0.02-0.66 microg/L) whereas 8 of 43 BALFs from patients (median 0, range 0-0.64 microg/L, P = 0.0001) contained TATI. Patient BALFs showed significantly increased activation of MMP-9 and MMP-8 compared with healthy controls. The concentrations of trypsin-2-alpha1-PI complex correlated with the in vivo activation of MMP-9 and -8 (r = 0.68, P = 0.002 and r = 0.61, P = 0.008) but not with the activation of MMP-2 in BALFs.


CONCLUSIONS
Results show a key role of trypsin-2 in the in vivo activation of proMMP-8 and -9 in inflammatory lung diseases.
Prikk
K
K
Department of Pulmonology, University of Tartu, Riia, Estonia. prikk@hammas.helsinki.fi
Maisi
P
P
Sepper
R
R
Stenman
U H
UH
Salo
T
T
Sorsa
T
T
D000328:Adult; D015153:Blotting, Western; D001987:Bronchiectasis / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D002648:Child; D006801:Humans; D007150:Immunohistochemistry; D008171:Lung Diseases / Q000201:enzymology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism; D014357:Trypsin / Q000502:physiology*; D014359:Trypsin Inhibitor, Kazal Pancreatic / Q000032:analysis*
D014359:Trypsin Inhibitor, Kazal Pancreatic; D014357:Trypsin; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9