Immunohistochemical localisation of the matrix metalloproteinases MMP-3 and MMP-9 within the airways in asthma

BACKGROUND The matrix metalloproteinase (MMP) enzymes MMP-3 and MMP-9 have relevance to the chronic structural airway changes in asthma. These proteinases can be generated by structural and inflammatory cells, and have the ability to degrade proteoglycans and thus potentially enhance airway fibrosis and smooth muscle proliferation through their ability to release and activate latent matrix bound growth factors. METHODS Immunostaining for MMP-3 and MMP-9 as well as for mast cells, eosinophils, and neutrophils was undertaken in acetone fixed and glycolmethacrylate embedded endobronchial biopsy specimens obtained by fibreoptic bronchoscopy under local anaesthesia. The findings from 17 asthmatic subjects (nine with mild to moderate non-steroid treated asthma and eight with chronic persistent steroid-dependent asthma) were compared with those from eight healthy controls. The cell associated MMP immunoreactivity was co-localised to mast cells, eosinophils, or neutrophils and represented as cells/mm2, based on the area of the biopsy specimen. Extracellular matrix immunoreactivity was assessed by an image analysis system and visually with ranking and the two approaches were compared. RESULTS The biopsy specimens from asthmatic subjects contained significantly more eosinophils (p