Differential expression of fibronectin and chronic lung injury by
anthropogenic combustion particles in three rat strains.
Kodavanti, Urmila P., Richard H. Jaskot, Wei Yi Su, Daniel L. Costa,
Andrew J. Ghio, and Kevin L. Dreher.
Pulmonary Toxicology Branch, Experimental Toxicology Division,
Human Studies Division, National Health and Environmental Effects
Research Laboratory, U S Environmental Protection Agency, Research
Triangle Park, NC 27711 and Duke University Medical Center, Durham,
NC, 27710
APStracts 3:0219L, 1996.
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 (F344) rats (60 d
old) were exposed to saline or ROFA, 8.3 mg/kg, by intratracheal (IT)
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 d post-exposure. Trichrome staining (TS) of the
lung sections indicated a sporadic incidence of focal alveolar
fibrosis at 1, 3, and 12 wk in SD rats, whereas WIS and F344 rats
showed only a modest increase in TS in the septal areas. Of all Fn
mRNA isoforms examined by PCR, only EIIIA(&) was up regulated
during 6 h -1 wk in ROFA-exposed SD and WIS but not in F344 rats. In
situ hybridization analysis in SD rats revealed Fn mRNA expression by
macrophage, 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 into discernible alveolar fibrosis. There is a rat
strain variation in ROFA-induced fibrosis and associated Fn
EIIIA(&) expression.
Received 19 December 1995; accepted in final form 15 October
1996.
APS Manuscript Number L373-5.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996