MINERAL DUSTS CAUSE ELASTIN AND COLLAGEN BREAKDOWN IN THE RAT LUNG - A POTENTIAL MECHANISM OF DUST-INDUCED EMPHYSEMA

It is now accepted that workers with exposure to mineral dusts can dev elop airflow obstruction. The basis of this process is uncertain, but carefully performed morphologic stud ies suggest that coal, silica, an d perhaps other dusts may produce emphysema in humans. To investigate the mechanisms involved in this process, we administered crystalline s ilica (quartz) or titanium dioxide (rutile) to rats in a single intrat racheal instillation. At varying times after instillation, the animals ' lungs were lavaged, the lavageate from one lung was dried and hydrol yzed, and the amounts of desmosine (DES), as a measure of elastin brea kdown, and hydroxyproline (HP), as a measure of collagen breakdown, we re determined. The lavageate from the other lung was counted for infla mmatory cells. Both silica and titanium dioxide caused a dose-dependen t increase in DES and HP 24 h after instillation. When an equivalent d ose (30 mg) of silica or rutile was administered and animals were sacr ificed at various times up to 21 d, a sustained increase in lavage DES and HP was seen in the silica-treated animals, and this was accompani ed by a sustained increase in polymorphonuclear leukocytes (PMN); in c ontrast, both lavage PMN and ravage DES/HP rapidly peaked and then dec lined in the titanium dioxide-treated animals. Numbers of macrophages remained elevated over the 21-d period of sacrifice with both types of treatment. These data show for the first time that mineral dusts can cause connective-tissue breakdown in the lung, with the release of mat rix components into the alveolar spaces. The amount of connective-tiss ue breakdown appears to parallel the number of PMN but not the number of macrophages in the alveolar spaces, suggesting that PMN-derived pro teolytic enzymes are responsible for the breakdown. This process proba bly plays a role in dust-induced emphysema.