MECHANISMS OF MINERAL DUST-INDUCED EMPHYSEMA

Mineral dust exposure can result in emphysema and chronic airflow obst ruction. We postulated that dust-induced emphysema has a pathogenesis similar to that in cigarette smoke-induced emphysema, namely, excess r elease of proteolytic enzymes from dust-evoked inflammatory cells, and inactivation of alpha-1-antitrypsin (A1AT) by dust-catalyzed formatio n of oxidants. To test this theory we examined the antiproteolytic act ivity of A1AT exposed to quartz in vitro and found that it was decreas ed in a dose-response fashion. Catalase prevented this effect, which s uggested that it was mediated by quartz-generated hydrogen peroxide. W t: also showed that a variety of dusts could oxidize methionine to met hionine sulfoxioe in vitro, using either pure amino acid or whole prot ein. The relative order of activity was coal > quartz > titanium dioxi de. Lastly, we used a new high-performance liquid chromatography techn ique to demonstrate that quartz, coal, and titanium dioxide produced c onnective tissue breakdown in rat lungs, as determined by the appearan ce of desmosine and hydroxyproline in lavage fluid after dust instilla tion. On a particle-for-particle basis, the order of dust potency was similar to that for methionine oxidation. Connective tissue breakdown was associated with elevations of both polymorphonuclear leukocytes an d macrophages in lavage fluid, and it is unclear whether one or both o f these types of inflammatory cell mediates this process. These observ ations support our theory that dust-induced emphysema and smoke-induce d emphysema occur through similar mechanisms.