Overexpression of matrix metalloproteinase‐8 and ‐9 in bronchiectatic airwaysin vivo

Abstract

The progressive bronchial dilatation in bronchiectasis is likely to be the result of continued airway matrix destruction, although little is known about the role of neutrophil matrix metalloproteinases (MMPs) in this process.Immunohistochemistry has been used to investigate the expression and cellular localisation of MMP-8 and MMP-9 in bronchiectatic airways in vivo. Endobronchial biopsies were taken from 25 bronchiectatic patients, and from the right lower lobe in 14 control subjects. MMP-8, MMP-9, neutrophils and macrophages were stained with monoclonal antibodies and quantified as positive cell?mm -2 of the lamina propria by using an image analysis system.There were significantly higher densities of MMP-8 and MMP-9 positive cells in the lamina propria of bronchiectatic than control airways. In bronchiectatic airways, the densities of MMP-8 and MMP-9 positive cells correlated with each other and with neutrophil density, but not with macrophage density. In control airways, a significant correlation was found between MMP-8 with neutrophil and MMP-9 with macrophage densities.An overexpression of neutrophil matrix metalloproteinases in bronchiectatic airways could help explain the continuation of airway destruction in bronchiectasis. In view of the clinical availability of matrix metalloproteinase antagonists, the results presented here could have a significant impact on the development of novel therapies of this untreatable disease.

Is cystic fibrosis a TH17 disease?

“…Currently, we know that chronic infection and inflammation in patients with CF is associated with progressive airways obstruction and bronchiectasis of the cartilaginous airways [1]. MMP2, 8 and 9 have been shown to be elevated in patients with bronchiectasis [65][66], but the processes and the specific cells involved in the destruction of airway cartilage and subsequent development of bronchiectasis are poorly understood. Based on the biological plausibility and current lack of explanation for the elevated MMPs and bronchiectasis in CF, it is tempting to speculate that IL-17 is a critical component in this process.…”

Mucosal inflammation in idiopathic bronchiectasis: cellular and molecular mechanisms

“…Increased levels of MMP-8 and MMP-9 have been reported in BAL fluid of subjects with bronchiectasis [103,104]. MMP-8 and MMP-9 expression in the bronchiectasis airways correlate significantly with airway neutrophil numbers but not with lung function and extension of disease [105].…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…Finally, MMP-8 levels in BALF also correlate with the severity of bronchiectasis, a disease characterized by a permanent dilation of the bronchi due to chronic inflammation, leading to irreparable deformation of bronchial wall components (Sepper et al, 1995). Other studies identified activated epithelial cells (as well as infiltrating neutrophils and macrophages) as the cell types responsible for the de novo MMP-8 expression in the course of this pathology (Prikk et al, 2001;Zheng et al, 2002).…”