Quartz inactivates alpha 1-antiproteinase: possible role in mineral dust-induced emphysema.
Occupational exposure to some types of mineral particles has been shown to be associated with the development of emphysema, but the mechanism of this process is unknown. Because many mineral particles are known to catalyze the formation of active oxygen species in aqueous solution, we hypothesized that mineral particles could oxidatively inactive antiproteinases, leading to an imbalance between protease and antiprotease activities, events similar to those believed to occur with cigarette smoke. To test this hypothesis, human alpha 1-antiproteinase (alpha 1-AP) was incubated with suspensions of freshly ground or aged quartz, and antiproteolytic activity was determined by using porcine pancreatic elastase. Increasing concentrations of quartz were associated with increasing losses of antiproteolytic activity; this effect could be prevented by catalase. Freshly ground quartz was more active than aged quartz. Western blot analysis for alpha 1-AP showed abnormal banding, suggesting that porcine pancreatic elastase-alpha 1-AP complex formation was impaired by silica exposure. Chemical assay of aqueous quartz suspensions demonstrated production of hydrogen peroxide; incubation of alpha 1-AP with hydrogen peroxide caused a dose-dependent loss of antiproteolytic activity, and this also could be prevented by catalase. We conclude that, at least in vitro, quartz can inactivate alpha 1-AP through a hydrogen peroxide-mediated mechanism and that oxidative loss of antiproteinase activity could play a role in mineral dust-induced emphysema.
Zay
K
K
Department of Pathology, University of British Columbia, Vancouver, Canada.
Devine
D
D
Churg
A
A
D000818:Animals; D015153:Blotting, Western; D002374:Catalase / Q000494:pharmacology; D004391:Dust / Q000009:adverse effects*; D004646:Emphysema / Q000139:chemically induced / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000037:antagonists & inhibitors; D011791:Quartz / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012822:Silicon Dioxide; D013552:Swine; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D004391:Dust; D005609:Free Radicals; D017382:Reactive Oxygen Species; D000515:alpha 1-Antitrypsin; D011791:Quartz; D012822:Silicon Dioxide; D006861:Hydrogen Peroxide; D002374:Catalase; D010196:Pancreatic Elastase