title: Airway obstruction correlates with collagenase-2 (MMP-8) expression and activation in bronchial asthma.
abstract: Matrix metalloproteinases (MMPs) contribute to extracellular matrix and basement membrane degradation in asthma. The present study analyzed molecular forms and degree of activation and expression of MMP-8 in bronchoalveolar lavage fluid (BALF), BALF cells, and bronchial tissue specimens from 14 steroid-naive asthma patients, 13 uncontrolled severe asthma patients, 13 controlled asthma patients, and 14 healthy subjects by Western immunoblotting, immunohistochemistry, and in situ hybridization. Immunohistochemistry and in situ hybridization revealed a prominent MMP-8 immunoreactivity in submucosal inflammatory, glandular, and shed, but not in intact bronchial epithelial cells of asthma patients. In BALF cytospins, both MMP-8 protein and mRNA expression were observed in epithelial cells, macrophages, and polymorphonuclear leukocytes (PMNs). MMP-8 was present in BALFs asthma patients in complex, pro- and active PMN-type, and pro- and active non-PMN-type forms. BALF MMP-8 was significantly converted to active form only in BALFs from steroid-naive and uncontrolled severe asthma patients, but not in BALFs from well-controlled asthma patients or healthy controls. A significant inverse correlation between BALF MMP-8 levels and FEV1 (r = -0.283, p = 0.04), and BALF activated MMP-8 forms and FEV1 (r = -0.427, p = 0.001) was detected. Overall, these data suggest that MMP-8 and its activation has an important role in the airway destruction, healing, remodeling, and treatment response in asthma.
authors.affiliation: Institute of Experimental and Clinical Medicine, Tallinn, Estonia. kaiu.prikk@helsinki.fi
authors.forename: Kaiu
authors.initials: K
authors.lastname: Prikk
authors.forename: Päivi
authors.initials: P
authors.lastname: Maisi
authors.forename: Emma
authors.initials: E
authors.lastname: Pirilä
authors.forename: Mari-Ann
authors.initials: MA
authors.lastname: Reintam
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
authors.forename: Ruth
authors.initials: R
authors.lastname: Sepper
mesh_terms: D000328:Adult; D000402:Airway Obstruction / Q000201:enzymology*; D001249:Asthma / Q000201:enzymology* / Q000503:physiopathology; D015153:Blotting, Western; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004789:Enzyme Activation; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000032:analysis* / Q000235:genetics; D008875:Middle Aged; D012333:RNA, Messenger / Q000032:analysis
chemical_list: D012333:RNA, Messenger; D020784:Matrix Metalloproteinase 8