AJP - Lung Cellular and Molecular Physiology, Vol 272, Issue 3 521-L532, Copyright © 1997 by American Physiological Society

ARTICLES

Genetic variability in combustion particle-induced chronic lung injury

U. P. Kodavanti, R. H. Jaskot, W. Y. Su, D. L. Costa, A. J. Ghio and K. L. Dreher
Experimental Toxicology Division, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

Occupational exposure to anthropogenic particles is associated with lung injury in humans. We hypothesized that residual oil fly ash (ROFA), an emission source particulate, may induce acute lung injury and fibrosis in sensitive rat strains and that fibronectin (Fn) gene expression will correspond to the development of fibrosis. Male Sprague-Dawley (SD), Wistar (WIS), and Fischer 344 (F-344) rats (60 days old) were exposed to saline or ROFA (8.3 mg/kg) by intratracheal instillation and examined for up to 12 wk. Histology indicated focal areas of lung damage showing inflammatory cell infiltration as well as alveolar, airway, and interstitial thickening in all three rat strains during 1-7 days postexposure. Trichrome staining of the lung sections indicated a sporadic incidence of focal alveolar fibrosis at 1, 3, and 12 wk in SD rats, whereas WIS and F-344 rats showed only a modest increase in trichrome staining in the septal areas. Of all Fn mRNA isoforms examined by polymerase chain reaction, only EIIIA(+) was upregulated during 6 h-1 wk in ROFA-exposed SD and WIS rats but not in F-344 rats. In situ hybridization analysis in SD rats revealed Fn mRNA expression by macrophage and alveolar and airway epithelium and within fibrotic areas. Immunohistochemical analysis revealed increased presence of Fn EIIIA(+) protein in the areas of fibrotic injury and basally to the airway epithelium. In summary, Fn EIIIA(+) increases early in the course of particle-induced lung injury and remodeling, which may or may not result in discernible alveolar fibrosis. There is a rat strain variation in ROFA-induced fibrosis and associated Fn EIIIA(+) expression.

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