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The Proceedings of the American Thoracic Society 5:375 (2008)
© 2008 The American Thoracic Society
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Remodeling of the Respiratory Unit in Silica-exposed Mice

Cheryl L. Fattman1, German Torres1, Brian L. Brockway2, Barry R. Stripp2 and Luis A. Ortiz1

1 Department of Environmental and Occupational Health, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania; and 2 Department of Pulmonary Medicine, Duke University, Durham, North Carolina

Correspondence and requests for reprints should be addressed to Cheryl L. Fattman, Ph.D., Department of Environmental and Occupational Health, Bridgeside Point, Suite 350, 100 Technology Drive, Pittsburgh, PA 15219. E-mail: cfattman{at}pitt.edu

Silicosis is a progressively debilitating disease for which there is no effective therapy. The pathologic remodeling of the silicotic lung is characterized by bronchiolar- and alveolar-localized inflammatory cell recruitment and tissue fibrosis. Previous studies demonstrate that tissue remodeling mediated by an aberrant or inadequate CCSP-expressing population of lung progenitor cells may exacerbate other types of lung disease. Here we hypothesize that silica exposure negatively impacts the reparative properties of the distal airway epithelium, resulting in alveolar dysfunction and exacerbation of silicotic lung disease. In our model, a single intratracheal injection of 0.2 g/kg silica into mice results in an inflammatory reaction that develops approximately 1 to 3 days after initial deposition. Analysis of bronchoalveolar lavage fluid from silica-treated mice at this time shows a significant neutrophil influx as well as increased total protein content, as compared with saline-treated control mice, that is indicative of acute lung injury. The effect of silica deposition on the fate of epithelial cells within terminal bronchioles was assessed through analysis of CCSP-immunoreactive cells as a measure of stem and progenitor cells. We observed a noticeable disorganization of CCSP-expressing cells and reduced overall CCSP content in the terminal bronchioles of silica-treated mice. These data support our hypothesis that silica exposure alters the phenotype of epithelial cells in bronchiolar airways.

FOOTNOTES

Supported by grants from the National Institute of Envrionmental Health Science (K22ES012269 to C.L.F. and RO1ESo10859 to L.A.O.).

Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript.

(Received in original form January 3, 2008; accepted in final form January 4, 2008)





This Article
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Right arrow Articles by Fattman, C. L.
Right arrow Articles by Ortiz, L. A.
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Right arrow Articles by Fattman, C. L.
Right arrow Articles by Ortiz, L. A.

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