Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat
Article first published online: 5 FEB 2001
Copyright © 2001 John Wiley & Sons, Ltd.
The Journal of Pathology
Volume 193, Issue 4, pages 538–545, April 2001
How to Cite
Corbel, M., Caulet-Maugendre, S., Germain, N., Molet, S., Lagente, V. and Boichot, E. (2001), Inhibition of bleomycin-induced pulmonary fibrosis in mice by the matrix metalloproteinase inhibitor batimastat. J. Pathol., 193: 538–545. doi: 10.1002/path.826
- Issue published online: 21 MAR 2001
- Article first published online: 5 FEB 2001
- Manuscript Accepted: 11 OCT 2000
- Manuscript Revised: 20 SEP 2000
- Manuscript Received: 1 JUN 2000
- Conseil Régional de Bretagne, France
- matrix metalloproteinase;
Bleomycin-induced pulmonary fibrosis is known to be associated with the increased activity of two gelatinases, matrix metalloproteinase (MMP)-2 and MMP-9, in bronchoalveolar lavage (BAL). This study has investigated the effect of a synthetic inhibitor of MMP, batimastat, on the development of pulmonary fibrosis induced by bleomycin administration in mice. Animals wereintranasally instilled with saline or bleomycin (0.5 mg in 100 µl per mouse). Batimastat (30 mg/kg) or vehicle alone was administered by intraperitoneal injection 24 h and 1 h before saline or bleomycin instillation, and then daily at the same dosage until the end of the study. Fifteen days after bleomycin administration, BAL was performed and the lung was removed. Treatment of mice with batimastat significantly reduced bleomycin-induced lung fibrosis, as shown in the lung by histopathological examination and by a decrease in hydroxyproline levels. Batimastat also prevented the increase in BAL macrophage and lymphocyte numbers, whereas it did not show any effect on the increased expression of active transforming growth factor-beta (TGF-β) in BAL. Batimastat treatment was effective in reducing MMP-2 and MMP-9 activity as well as the tissue inhibitor of metalloproteinase-1 (TIMP-1) level in BAL. These results suggest that administration of the MMP inhibitor batimastat is useful in preventing experimental pulmonary fibrosis induced by bleomycin and raises the possibility of a therapeutic approach to human pulmonary fibrotic disease. Copyright © 2001 John Wiley & Sons, Ltd.