INCREASED ELASTIN PRODUCTION IN EXPERIMENTAL GRANULOMATOUS LUNG-DISEASE

In the normal, healthy lung, elastin production is restricted to perio ds of development and growth. However, elastin expression irt the adul t lung has been observed in some forms of pulmonary injury, including pulmonary fibrosis. Here, we report that elastin production Is signifi cantly increased within precise interstitial compartments of the lung in an experimental model of granulomatous lung disease. An increase in the number and volume of elastic fibers within the alveolar walls was apparent on histological examination of Verhoeff-van Gieson-stained s ections of silicotic mt lungs. Quantitation of mature elastin cross-li nks indicated that silicosis was accompanied by a 17-fold increase in lung elastin content when compared with values from saline-treated con trols. In situ hybridization for tropoelastin mRNA revealed that elast in production was absent from granulomatous lesions yet was prominent at nonfibrotic alveolar septal tips, where a high density of elastic f ibers is seen in the normal lung. Immunohistochemistry indicated tropo elastin was being expressed by alpha-smooth muscle actin-containing ce lls. Transforming growth factor-beta was immunolocalized to granulomat ous regions of the silicotic lung bat was absent from regions showing increased tropoelastin expression. These data indicate that the reinit iation of tropoelastin gene expression is associated with granulomatou s lung disease, and this expression lends to the aberrant accumulation of mature elastin in the lung.