Soluble membrane-type 1 matrix metalloproteinase (MT1-MMP) and gelatinase A (MMP-2) in induced sputum and bronchoalveolar lavage fluid of human bronchial asthma and bronchiectasis.
The aim of this study was to investigate the involvement of the MT1-MMP/MMP-2 cascade in induced sputum (IS) and bronchoalveolar lavage fluid (BALF) from bronchial asthma (BA) and bronchiectasis (BE) patients and healthy controls. The molecular forms and cellular origins of MT1-MMP and MMP-2 were determined by Western immunoblotting, immunohistochemistry and in situ hybridization. Elevated levels of soluble activated and autocatalyzed MT1-MMP species as well as activated forms of MMP-2 in IS and BALF samples from BA and BE patients were evidenced. The activation degrees of soluble MT1-MMP and MMP-2 were significantly correlated in BA and BE IS and BALF. Only low levels of both these MMPs were observed in healthy control IS and BALF. The co-expression of MMP-2 with MT1-MMP was evidenced by double immunostaining in bronchial epithelial cells, submucosal glandular cells, smooth muscle cells and monocyte/macrophages. The MT1-MMP/MMP-2 cascade is present and active in human inflammatory lung disease fluid and tissue samples. This cascade seemingly reflects the active destructive phases of these chronic lung diseases.
Maisi
Päivi
P
Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland.
Prikk
Kaiu
K
Sepper
Ruth
R
Pirilä
Emma
E
Salo
Tuula
T
Hietanen
Jarkko
J
Sorsa
Timo
T
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000201:enzymology*; D015153:Blotting, Western; D001980:Bronchi / Q000201:enzymology; D001987:Bronchiectasis / Q000201:enzymology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry*; D004848:Epithelium / Q000201:enzymology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008264:Macrophages / Q000201:enzymology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000032:analysis / Q000378:metabolism*; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D013183:Sputum / Q000201:enzymology*
D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2