1. ¹Institute of Experimental and Clinical Medicine, Tallinn, Estonia, Finland
2. ²The North-Estonian Regional Hospital, Tallinn, Estonia, Finland
3. ³Department of Clinical Veterinary Sciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
4. ⁴Department of Oral and Maxillofacial Diseases, Institute of Dentistry, Helsinki University Central Hospital, University of Helsinki, Helsinki, Finland
5. ⁵Orton Research Institute and the Orthopaedic Hospital of Invalid Foundation, Helsinki, Finland
6. ⁶Departments of Oral Diagnostics and Pathology, University of Oulu, Oulu, Finland

Correspondence: Dr. Kaiu Prikk, c/o Dr Timo Sorsa, Oral Pathology Unit at Biomedicum Helsinki, 2nd floor, University of Helsinki, PL 63 (Haartmaninkatu 8), 00014 Helsinki, Finland. E-mail: kaiu.prikk@helsinki.fi

Received 9 July 2002.

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.