Image Analysis Quantitation of Type 2 Cells and Alveolar Walls Part II: Influence of 0.3 ppm Nitrogen Dioxide Exposure on the Developing Mouse Lung

Abstract

Newborn male mice (45 control and 45 experimental) were tested after 6 weeks of 0.3 ppm nitrogen dioxide (NO2) exposure and at postexposure periods of 4 and 10 weeks. After 6 weeks of exposure, there was a 12.9% increase in type 2 cell number that was statistically significant (P < 0.025) and an 11% increase in mean type 2 cell area that fell short of statistical significance. The ratio of cell area to alveolar wall area was also statistically significant (P = 0.05). The latter ratio, dividing a combined measurement of numbers and area of type 2 cells (type 2 cell field area) by the alveolar wall area, serves to control for lung volume. Although increases in type 2 cell number were not statistically significant for the 2 postexposure test periods, a significant increase (P < 0.05) was found by analysis of variance for all 3 test periods. NO2 exposure also resulted in a significant interaction (group x time; P < 0.05) of the type 2 cell field area:alveolar wall area ratio, i.e., a progressive fall for the exposed animals vs. a progressive rise for the control group. The interaction is believed to be the result of NO2-induced type 2 cell swelling followed by impairment of normal type 2 cell growth. The increase in type 2 cell numbers most likely reflects damage to the type 1 cell population since type 2 cell hyperplasia is a common denominator for diverse kinds of human lung disease where damaged type 1 cells are replaced by type 2 cells. The finding of a statistically significant interaction of the type 2 cell field area:wall area ratio and the persistence of increased alveolar wall area imply that the effects of NO2 on type 2 cells and alveolar walls were not completely reversed 10 weeks after exposure. Should the effects be irreversible, there would be the further implication of a commensurate depletion of structural and functional reserves of the lung.