EMMPRIN (CD147) regulation of MMP‐9 in bronchial epithelial cells in COPD

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN or CD147) induces the production of matrix metalloproteinases (MMP) such as MMP-9, which plays an important role in COPD. We determined its cellular origin and role in MMP-9 production in COPD. Bronchial biopsies, alveolar macrophages (AM) and blood monocytes (BM) from patients with COPD, healthy smokers and non-smokers, and bronchial epithelial cells (EC) from surgically resected airways from patients with COPD were stimulated with LPS or CRP in the presence and absence of an anti-EMMPRIN blocking antibody. EMMPRIN in BAL, plasma, conditioned media and cell lysates was quantified and immunohistochemical localization of EMMPRIN was determined in bronchial biopsies. MMP-9 activity and mRNA was also determined. EMMPRIN levels in BAL fluid were higher in patients with COPD compared with non-smokers and smokers. There was greater EMMPRIN expression in EC from patients with COPD compared with smokers and non-smokers. EC secreted and expressed more EMMPRIN protein than BM and AM. Blocking EMMPRIN decreased MMP-9 activity in supernatant of EC, but not in those from AM and BM, and decreased MMP-9 mRNA expression in EC. The increased EMMPRIN expression in COPD is reflected by an increased release from bronchial EC, which are one of the main source of EMMPRIN. EMMPRIN regulates MMP-9 expression in COPD.