Matrix metalloproteinase-induction in fibrosis and fibrotic nodule formation due to silica inhalation.
Scabilloni-JF; Wang-L; Ramsey-DM; McLaurin-J; Castranova-V; Mercer-RR
Am J Respir Crit Care Med 2001 Apr; 163(5)(2)(Suppl):A169
Matrix Metalloproteinases (MMP) are the enzymes that initiate degradation of collagen. We examined the role of MMP's during alveolar wall fibrosis and fibrotic nodule formation due to silica exposure. Rats were exposed to 15 mg/m3 silica or filtered air for 5 days/week, 6 hours/day. Lungs were preserved by intra-tracheal instillation of fixative at 40, 60, 79 and 116 days of exposure. Additional rats were sacrificed for collagenase and zymographic assays. Tissue sections were processed for Sirius Red staining of collagen and immunohistochemistry detection of Stromelysin (MMP-10), Gelatinase A (MMP-2) Tissue Inhibitor of Metalloproteinase (TIMP-1) and TGF-B. The number of fibrotic nodules were determined by morphometric analysis. Fibrotic nodules were defined by a collagenous core and a bounding cell layer detached from the alveolar wall. At 79 and 116 days, exposed lungs show an increase of collagen in alveolar walls and fibrotic nodules.
Enzymes; Collagen-fibrils; Fibrosis; Silica-dusts; Exposure-levels; Animal-studies; Laboratory-animals
American Journal of Respiratory and Critical Care Medicine. Abstracts of the American Thoracic Society 2001 International Conference, May 18-23, 2001, San Francisco, California