Extracellular matrix metalloproteinase inducer in interstitial pneumonias

Abstract

Extracellular matrix metalloproteinase inducer (EMMPRIN), a glycosylated transmembrane protein that induces matrix metalloproteinases (MMPs), is minimally expressed in the normal adult lung. We previously reported that it is up-regulated in murine bleomycin-induced lung injury. In this study, we determined the expression of EMMPRIN and its association with MMP-2, MMP-7, and MMP-9 in interstitial pneumonias (IPs). We performed immunohistochemistry for EMMPRIN and MMPs on lung tissue from 22 subjects with various IPs. We did bronchoalveolar lavage (BAL) on 9 of these subjects and 13 others with IPs to measure the soluble EMMPRIN in BAL fluid. For comparison, immunohistochemistry or BAL was done on 14 subjects without IPs. The staining intensity for each protein was scored from 0 to 3 in various epithelial cell types. Soluble EMMPRIN in BAL fluid was measured by an enzyme-linked immunosorbent assay. Extracellular matrix metalloproteinase inducer was prominent in abnormal epithelial cells. It was more prominent in hyperplastic type II cells, compared with epithelium in alveolar bronchiolization. It was also elevated in BAL fluid from the subjects with IPs. Matrix metalloproteinases were expressed in cells expressing EMMPRIN, although the profile of MMPs varied among the different abnormal epithelial cell types with MMP-2 and MMP-7 in hyperplastic type II cells and MMP-7 and MMP-9 in cells showing squamous metaplasia and cells comprising bronchiolization. These results suggest a role of EMMPRIN in reepithelialization in IPs.