EFFECT OF INHALED CHROMIUM ON PULMONARY A1AT

Abstract

A major health hazard to coal miners is development of emphysema following long-term exposure to coal dust. One mechanism underlying development of emphysema is the oxidation of critical methionine (Met) residues in antiproteolytic factor,α 1-antitrypsin (A1AT) resulting in a protease-antiprotease imbalance in the lung. Several studies have documented an association between the incidence and severity of emphysema among miners and their exposure to crystalline silica (i.e., SiO 2) . However, what remains unclear is the role of other co-inhaled nonemphysematogenic nonoxidant inorganic constituent in disease pathogenesis. We hypothesize that in miners, inhaled trivalent chromium (Cr 3+, the only form of Cr in coal) may potentially affect lung A1AT activity in situ via Cr complexing with Met residues, and thereby exacerbate any SiO 2 -induced imbalance. To ascertain if Cr 3+ could, in fact, affect A1AT activity, in vitro studies were done to assess elastase inhibitory activity following A1AT incubation with soluble Cr 3+. In addition, to determine if Cr 3+ found in the lungs as detoxification products of inhaled hexavalent Cr (Cr 6+) could affect A1AT in situ, lavages from the lungs of chromate-exposed rats were also analyzed for elastase inhibitory activity. The in vitro results indicate that Cr 3+ ions clearly inhibited A1AT function, with an IC50 of 1.1 m M being estimated under the experimental conditions used. The in vivo results indicate that long-term inhalation (12 wk or longer) of chromate-bearing atmospheres also gave rise to significant (i.e., 50-70%) inhibition of the antielastase activity of A1AT. Together, these results clearly suggest that the Cr 3+ present in coal dusts could potentially act to inhibit A1AT activity in the lungs of miners and thereby promote the emphysematogenicity of SiO 2 or of other emphysematogens present as coconstituents in these dusts.