Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis

The role of various matrix metalloproteinases (MMP) and tissue Inhibitor of metalloprotelnases‐2 (TIMP‐2), and the gelatholytic activities of MMP involved in the process of bleomycin‐induced pulmonary fibrosis in rabbits were Investigated. Male Japanese white rabbits were intubated with tracheal tub...

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Bibliographic Details
Published in:	Pathology international Vol. 48; no. 12; pp. 954 - 963
Main Authors:	Yaguchi, Takamoto, Fukuda, Yuh, Ishizaki, Masamlchi, Yamanaka, Nobuaki
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-12-1998
Subjects:	Animals Bleomycin Collagenases - metabolism Gelatin - metabolism gelatin zymography Gelatinases - metabolism Immunohistochemistry Male matrix metallo-proteinase Matrix Metalloproteinase 1 Matrix Metalloproteinase 2 Matrix Metalloproteinase 9 Metalloendopeptidases - metabolism Microscopy, Electron pulmonary fibrosis Pulmonary Fibrosis - chemically induced Pulmonary Fibrosis - enzymology Pulmonary Fibrosis - pathology Rabbits Time Factors tissue inhibitor of matrix metalloproteinase Tissue Inhibitor of Metalloproteinase-2 - metabolism
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Summary:	The role of various matrix metalloproteinases (MMP) and tissue Inhibitor of metalloprotelnases‐2 (TIMP‐2), and the gelatholytic activities of MMP involved in the process of bleomycin‐induced pulmonary fibrosis in rabbits were Investigated. Male Japanese white rabbits were intubated with tracheal tubes under anesthesia, and bleomycin hydrochloride in sterile saline or only sterile saline was administered through the tracheal tubes. The animals were killed 1, 3, 7, 14 and 28 days after the administration of bleomycln (n = 3) or saline (n = 2). Light microscopic lmmunohistochemlstry for MMP‐1 (interstitial collagenase), MMPP (gelatinase A), MMP‐9 (gelatinase B) and TIMP‐2 was performed. The gelatinolytic activities of lung tissue homogenates were studied by gelatin zymography. In the early stages, the gelatholytic activity of MMP‐9 was predominant. MYP‐9 localized in the infiltrating neutrophils, macrophages, bronchial and bronchiolar epithelial cells. The alveolar epithelial basement membrane was frequently disrupted in the early stages, where MMP‐9 possibly contributed to the disruption. In the late stages, the gelatinolytic activities of the latent and active forms of MMP‐2 were predominant, and MMPP localized in the regenerated alveolar epithelial cells in addition to the bronchial epithelial cells. MMP‐2, especially its active form, possibly plays a role in alveolar epithelial cell regeneration. The localization of MMP‐1 was similar to that of MMP‐9. TIMP‐2 localized in the epithelial cells and in some fibroblasts in fibro tic lesions. TIMP‐2 possibly plays a role in extracellular matrix deposition in balance with MMP.
Bibliography:	ArticleID:PIN954 ark:/67375/WNG-2PKKCPCS-1 istex:F7C2B2FE0CBF5AE2C1BC7CF12323B047C8BBB862
ISSN:	1320-5463 1440-1827
DOI:	10.1111/j.1440-1827.1998.tb03866.x