Stromelysin is a collagenase of the matrix metalloprotease family that is involved in collagen remodeling of scar and wound tissues. It is not normally present in the lungs. In this study, we tested the hypothesis that the matrix metalloprotease, stromelysin, is induced by instillation of toxic particles into the lungs. Male, Fischer 344 rats (body weight 255+/-8 g, mean+/-SE, N=6) were intratracheally instilled with saline vehicle or 4 mg of either crystalline silica, titanium dioxide or particulates from air sampling of citrus and grape fields. After 4 weeks, rats were sacrificed and the lungs were analyzed for total lung collagenase activity using a fluorometric assay. Matrix metalloprotease 2 (MMP2, the principal form of collagenase normally present in the lungs) and stromelysin were localized using immunohistochemistry. Total lung collagenase activity was 407+/-130, 464+/-64, 644+/-110, 895+/-126 and 906+/-129 nmol substrate/min/lung (mean+/-SE, N=6) for saline, titanium dioxide, citrus, grape and silica treated lung, respectively. Total lung collagenase activities of citrus, grape and silica exposed lungs were significantly greater than saline and titanium dioxide treated lungs. Immunohistochemistry demonstrated significant expression of stromelysin in silica, citrus and grape instilled lungs. Stromelysin was not present in the saline controls or titanium dioxide treated lungs. MMP2 was significantly elevated above saline and/or titanium dioxide in silica, citrus and grape treated lungs. The results suggest that stromelysin may play a role in lung remodeling in response to toxic particles, and that it may be used to differentiate between toxic and non-toxic particles.
The Toxicologist. Society of Toxicology 42nd Annual Meeting and ToxExpo, Cutting-Edge Science, Networking, New Perspectives, March 9-13, 2003, Salt Lake City, Utah