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


METHODS
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.
Fujishima
Seitaro
S
Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan.
Shiomi
Takayuki
T
Yamashita
Shuji
S
Yogo
Yurika
Y
Nakano
Yasushi
Y
Inoue
Takashi
T
Nakamura
Morio
M
Tasaka
Sadatomo
S
Hasegawa
Naoki
N
Aikawa
Naoki
N
Ishizaka
Akitoshi
A
Okada
Yasunori
Y
D015415:Biomarkers / Q000378:metabolism; D055745:Bronchioles / Q000201:enzymology / Q000473:pathology; D018893:Bronchoalveolar Lavage; D006801:Humans; D054990:Idiopathic Pulmonary Fibrosis / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology* / Q000473:pathology; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000473:pathology; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D008875:Middle Aged; D020545:Respiratory Mucosa / Q000201:enzymology / Q000473:pathology
D015415:Biomarkers; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7