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 develop airflow obstruction. The basis of this process is uncertain, but carefully performed morphologic studies suggest that coal, silica, and perhaps other dusts may produce emphysema in humans. To investigate the mechanisms involved in this process, we administered crystalline silica (quartz) or titanium dioxide (rutile) to rats in a single intratracheal instillation. At varying times after instillation, the animals' lungs were lavaged, the lavageate from one lung was dried and hydrolyzed, and the amounts of desmosine (DES),as a measure of elastin breakdown, and hydroxyproline (HP), as a measure of collagen breakdown, were determined. The lavageate from the other lung was counted for inflammatory cells. Both silica and titanium dioxide caused a dose-dependent increase in DES and HP 24 h after instillation. When an equivalent dose (30 mg) of silica or rutile was administered and animals were sacrificed 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 accompanied by a sustained increase in polymorphonuclear leukocytes (PMN); in contrast, both lavage PMN and lavage DES/HP rapidly peaked and then declined 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 matrix components into the alveolar spaces. The amount of connective-tissue breakdown appears to parallel the number of PMN but not the number of macrophages in the alveolar spaces, suggesting that PMN-derived proteolytic enzymes are responsible for the breakdown. This process probably plays a role in dust-induced emphysema.
Li
K
K
Department of Pathology, University of British Columbia, Vancouver, Canada.
Keeling
B
B
Churg
A
A
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003094:Collagen / Q000378:metabolism*; D003895:Desmosine / Q000032:analysis; D004391:Dust / Q000009:adverse effects*; D004549:Elastin / Q000378:metabolism*; D006909:Hydroxyproline / Q000032:analysis; D007249:Inflammation; D008168:Lung / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008903:Minerals; D011656:Pulmonary Emphysema / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D011791:Quartz; D051381:Rats; D017207:Rats, Sprague-Dawley; D014025:Titanium
D004391:Dust; D008903:Minerals; D003895:Desmosine; D011791:Quartz; C009495:titanium dioxide; D003094:Collagen; D004549:Elastin; D014025:Titanium; D006909:Hydroxyproline