Respiratory tract lesions induced by sulfur mustard (SM), a chemical warfare agent, are characterized by epithelial damage associated with inflammatory cell infiltration. To test the potential role of matrix metalloproteinase gelatinases in these lesions, we evaluated gelatinase activity, albumin content, and total cell count in bronchoalveolar lavage fluid of guinea pigs 24 h after an intratracheal injection of 0.2 mg/kg of SM. The bronchial lavage and alveolar lavage fluids were analyzed separately. The increase in inflammatory cell content of the bronchial lavage fluid, mainly macrophages, observed in SM-intoxicated guinea pigs was accompanied by an increase in albumin and in 92-kDa gelatinase activity. There was a significant correlation between albumin content and 92-kDa gelatinase activity (r = 0.67) and between 92-kDa gelatinase and the number of macrophages. Immunohistochemistry performed on tracheal sections showed the presence of 92-kDa gelatinase at the site of intraepithelial cleavages. Zymography analysis of culture medium conditioned by guinea pig tracheal epithelial cells demonstrated that these cells produced in vitro 92-kDa gelatinase on stimulation. Culture of human bronchial epithelial cells obtained by the explant technique showed a marked increase in 92-kDa gelatinase after exposure to 5 × 10⁵ M SM that reinforced the relevance of our animal results to human exposure to SM. These results suggest that in SM respiratory intoxication, 92-kDa gelatinase of both inflammatory and epithelial cell origins could be involved in epithelial cell detachment.

vesicant agents; proteases; bronchoalveolar lavage; macrophages

This article has been cited by other articles:

				C. Guignabert, L. Taysse, J.-H. Calvet, E. Planus, S. Delamanche, S. Galiacy, and M.-P. d'Ortho Effect of doxycycline on sulfur mustard-induced respiratory lesions in guinea pigs Am J Physiol Lung Cell Mol Physiol, July 1, 2005; 289(1): L67 - L74. [Abstract] [Full Text] [PDF]

				Y. Morishima, A. Nomura, Y. Uchida, Y. Noguchi, T. Sakamoto, Y. Ishii, Y. Goto, K. Masuyama, M. J. Zhang, K. Hirano, et al. Triggering the Induction of Myofibroblast and Fibrogenesis by Airway Epithelial Shedding Am. J. Respir. Cell Mol. Biol., January 1, 2001; 24(1): 1 - 11. [Abstract] [Full Text]

				S. Rappeneau, A. Baeza-Squiban, F. Marano, and J.-H. Calvet Efficient Protection of Human Bronchial Epithelial Cells against Sulfur and Nitrogen Mustard Cytotoxicity Using Drug Combinations Toxicol. Sci., November 1, 2000; 58(1): 153 - 160. [Abstract] [Full Text] [PDF]