1. EFFECT OF INHALED CHROMIUM ON PULMONARY A1AT.
- Author
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Cohen, Mitchell D., Sisco, Maureen, Baker, Kathy, Chen, Lung-Chi, and Schlesinger, Richard B.
- Subjects
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PULMONARY emphysema , *CHROMIUM , *PROTEOLYTIC enzymes , *COAL miners - 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, α1-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[sub 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[sup 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[sub 2]-induced imbalance. To ascertain if Cr[sup 3+] could, in fact, affect A1AT activity, in vitro studies were done to assess elastase inhibitory activity following A1AT incubation with soluble Cr[sup 3+]. In addition, to determine if Cr[sup 3+] found in the lungs as detoxification products of inhaled hexavalent Cr (Cr[sup 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[sup 3+] ions clearly inhibited A1AT function, with an IC50 of 1.1 mM 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[sup 3+] present in coal dusts could potentially act to inhibit A1AT activity in the lungs of miners and thereby promote the emphysematogenicity of SiO[sub 2] or of other emphysematogens present as coconstituents in these dusts. [ABSTRACT FROM AUTHOR]
- Published
- 2002
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