In vivo collagenase-2 (MMP-8) expression by human bronchial epithelial cells and monocytes/macrophages in bronchiectasis

Abstract

The purpose of this study was to determine whether other cellular sources than neutrophils can express matrix metalloproteinase (MMP)‐8 protein and mRNA in bronchiectatic (BE) lung. The molecular forms of MMP‐8 in the BE bronchoalveolar lavage fluid (BALF) and healthy control BALF were analysed by western immunoblotting. MMP‐8 expression was demonstrated by immunohistochemistry and in situ hybridization in BE lung tissue and by immunohistochemistry in control lung tissue. In the BE BALF, different MMP‐8 species were detected: 70–80 kD MMP‐8 apparently of polymorphonuclear leukocyte (PMN) origin and also 40–60 kD MMP‐8 from non‐PMN cellular sources, such as bronchial epithelial cells, glandular cells or monocytes/macrophages. Both of these MMP‐8 species were elevated and converted to a significant extent to activated forms in BE BALF compared with healthy control BALF. The levels of high molecular weight (>80 kD) MMP‐8 complexes, evidently representing MMP‐8 trapped by endogenous MMP inhibitors and/or MMP‐8 dimers, were significantly elevated in BE BALF compared with healthy control BALF. In BE lung tissue, the MMP‐8 protein and mRNA expression was found in bronchial ciliated epithelial cells, glandular cells, neutrophils, and monocytes/macrophages infiltrating the bronchial epithelial area. Minimal MMP‐8 expression was observed in neutrophils, monocytes/macrophages, and epithelial cells in control lung tissues. In this study, new potential cellular sources have been demonstrated for MMP‐8 in the inflamed lung. MMP‐8 from multiple cellular sources, including inflamed lung epithelium, was activated to a significant extent in the BE BALF, indicating a major role for MMP‐8 in the destruction of lung and bronchial tissues. Copyright © 2001 John Wiley & Sons, Ltd.