Centriacinar remodeling and sustained procollagen gene expression after exposure to ozone and nitrogen dioxide

Sprague-Dawley rats were exposed to 0.8 ppm ozone (O-3) to 14.4 ppm nitroge n dioxide (NO2), or to both gases simultaneously for 6 h per day for up to 90 d. The extent of histopathologic changes within the central acinus of th e lungs was compared after 7 or 78 to 90 d of exposure using morphometric a nalysis by placement of concentric arcs radiating outward from a single ref erence point at the level of the bronchiole-alveolar duct junction. Lesions in the lungs of rats exposed to the mixture of gases extended approximatel y twice as far into the acinus as in those exposed to each individual gas. The extent of tissue involvement was the same at 78 to 90 d as noted at 7 d in all exposure groups. At the end of exposure, in situ hybridization for procollagen types I and III demonstrated high levels of messenger RNA withi n central acini in the lungs of animals exposed to the combination of O-3 a nd NO2 In contrast, animals exposed to each individual gas had a similar pa ttern of message expression compared with that seen in control animals, alt hough centriacinar histologic changes were still significantly different fr om control animals. We conclude that the progressive pulmonary fibrosis tha t occurs in rats exposed to the combination of O-3 and NO2 is due to sustai ned, elevated expression of the genes for procollagen types I and III. This effect at the gene level is correlated with the more severe histologic les ions seen in animals exposed to both O-3 and NO2 compared with those expose d to each individual gas. In contrast, the sustained expression of the proc ollagen genes is not associated with a shift in the distribution of the les ions because the area of change in each soup after 7 d of exposure was the same as after 78 to 90 d of exposure.