Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin

Tomoko Betsuyaku, Yuh Fukuda, William C. Parks, J. Michael Shipley, Robert M. Senior

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Abstract

Increased expression of matrix metalloproteinases, particularly gelatinase B (MMP-9), has been described in the lungs in pulmonary fibrosis. Intratracheal bleomycin is often used experimentally to produce lesions resembling human fibrosing alveolitis. To assess the role of gelatinase B in bleomycin-induced fibrosing alveolitis, we instilled bleomycin intratracheally into gelatinase B-deficient mice and gelatinase B+/+ littermates. Twenty-one days after bleomycin the two groups of mice were indistinguishable in terms of pulmonary histology and total lung collagen and elastin. However, the lungs of gelatinase B-deficient mice showed minimal alveolar bronchiolization, whereas bronchiolization was prominent in the lungs of gelatinase B+/+ mice. Gelatinase B was identified immunohistochemically in terminal bronchiolar cells and bronchiolized Cells 7 and 14 days after bleomycin in gelatinase B+/+ mice, and whole lung gelatinase B mRNA was increased at the same times. Many bronchiolized cells displayed Clara cell features by electron microscopy. Some bronchiolized cells stained with antibody tO helix transcription factor 4, a factor associated with the ciliated cell phenotype. Thus, fibrosing alveolitis develops after intratracheal bleomycin irrespective of gelatinase B. However, gelattnase B is required for alveolar bronchiolization, perhaps by facilitating migration of Clara cells and other bronchiolar cells into the regions of alveolar injury.

Original languageEnglish
Article number64563
Pages (from-to)525-535
Number of pages11
JournalAmerican Journal of Pathology
Volume157
Issue number2
DOIs
Publication statusPublished - 2000 Jan 1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Betsuyaku, T., Fukuda, Y., Parks, W. C., Shipley, J. M., & Senior, R. M. (2000). Gelatinase B is required for alveolar bronchiolization after intratracheal bleomycin. American Journal of Pathology, 157(2), 525-535. [64563]. https://doi.org/10.1016/S0002-9440(10)64563-4