Molecular determinants of organic dust exposures in respiratory cells.
Cosma-G; Martinez-A; Ufferfilge-D; Beard-M; Vallyathan-V; Olenchock-S
Toxicologist 1996 Mar; 30(1)(Part 2):273
We are utilizing a cell model to explore the pro-inflammatory responses of rat alveolar macrophages (AM) and respiratory epithelial cells to aqueous extracts of respirable grain dusts collected during routine agricultural operations. These studies are aimed at elucidating the underlying mechanisms of pulmonary injury and adaptation in agricultural workers exposed to organic dusts. Exposure to grain dusts or purified bacterial endotoxin/LPS resulted in a dose-dependent inhibition of cell growth in both AM and epithelial cell lines. Comparison of growth curves suggested the presence of other, unidentified, cytotoxic components of grain dusts, besides endotoxins. The inhibition of cell proliferation was preceded by the production of reactive oxygen species (ROS) in AM cells, measured by spectrophotometric determinations of hydrogen peroxide and superoxide anion, as well as by DNA fragmentation that is associated with apoptotic cell death, measured by DNA gel electrophoresis and ELISA. The comparative magnitudes of these proinflammatory responses suggest that the AM cells may be pivotal in producing toxicity in other respiratory cells following inhalation of organic dusts. We have also detected an immediate induction of the stress protein, metallothionein, in AM cells following their exposures to grain dust extracts and endotoxin. We are further studying the role of ROS in triggering apoptosis and whether metallothionein can inhibit ROS-related cell injury, as well as measuring the activation of the DNA transcription factor, NF-KB, in these cells following their exposures to organic dusts.
Organic-dusts; Respirable-dust; Occupational-exposure; Agriculture; Agricultural-industry; Models; Agricultural-workers; Pulmonary-system-disorders; Exposure-assessment; Endotoxins; Respiratory-system-disorders; Dusts; Dust-particles; Dust-exposure; Grain-dusts
The Toxicologist. Society of Toxicology 35th Annual Meeting, March 10-14,1996, Anaheim, California
Colorado State University