Journal
AMERICAN JOURNAL OF PATHOLOGY
Volume 157, Issue 2, Pages 525-535Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/S0002-9440(10)64563-4
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Funding
- NHLBI NIH HHS [HL47328, HL29594, R01 HL047328, P01 HL029594] Funding Source: Medline
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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, gelatinase B is required for alveolar bronchiolization, perhaps by facilitating migration of Clara cells and other bronchiolar cells into the regions of alveolar injury.
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