Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis

Seitaro Fujishima, Takayuki Shiomi, Shuji Yamashita, Yurika Yogo, Yasushi Nakano, Takashi Inoue, Morio Nakamura, Sadatomo Tasaka, Naoki Hasegawa, Naoki Aikawa, Akitoshi Ishizaka, Yasunori Okada

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46 Citations (Scopus)

Abstract

Context: Idiopathic pulmonary fibrosis (IPF) is characterized by diffuse interstitial inflammation and fibroblast proliferation with accelerated remodeling of extracellular matrix, which result in irreversible destruction of the lung's architecture. Objective: To elucidate the production levels, tissue localization, and activation of matrix metalloproteinase 7 (MMP-7) in the lungs of patients with IPF. Design: Bronchoalveolar lavage analysis was performed in 17 IPF patients and 6 healthy volunteers. Levels of MMP-7 in blood were assayed in 23 IPF patients and 20 controls. Histologic and immunohistochemical analyses were performed on paraffin sections of the lung tissues from patients with IPF, interstitial pneumonia associated with rheumatoid arthritis, or nonspecific interstitial pneumonia. Results: The proMMP-7 levels in bronchoalveolar lavage fluids from IPF patients were significantly higher than those from healthy controls, although there was no difference in the serum levels between the 2 groups. By immunohistochemistry, proMMP-7 was localized mainly to the hyperplastic alveolar and metaplastic bronchiolar epithelial cells in the lung tissues from IPF patients. Active MMP-7 was immunolocalized on alveolar macrophages and hyperplastic epithelial cells, which were also immunostained with antibody against CD151, a molecule associated with activation of proMMP-7. Immunoblot analysis indicated the overproduction of proMMP-7 together with a small amount of active MMP-7 in bronchoalveolar lavage fluids from IPF patients. The MMP-7 activity was detected in a cross-linked carboxymethylated transferrin film assay. Conclusions: proMMP-7 is excessively produced by hyperplastic alveolar and metaplastic bronchiolar epithelial cells and activated locally in the lungs of IPF patients, suggesting that MMP-7 may contribute to the pathology of IPF.

Original languageEnglish
Pages (from-to)1136-1142
Number of pages7
JournalArchives of Pathology and Laboratory Medicine
Volume134
Issue number8
Publication statusPublished - 2010 Aug 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

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    Fujishima, S., Shiomi, T., Yamashita, S., Yogo, Y., Nakano, Y., Inoue, T., Nakamura, M., Tasaka, S., Hasegawa, N., Aikawa, N., Ishizaka, A., & Okada, Y. (2010). Production and activation of matrix metalloproteinase 7 (matrilysin 1) in the lungs of patients with idiopathic pulmonary fibrosis. Archives of Pathology and Laboratory Medicine, 134(8), 1136-1142.