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 (NO,) 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. NO, 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 NO,-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 NO, 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.

Influence of Community Air Pollution on the Lungs of Mice. Part I: Hyperplasia and Hypertrophy of Type 2 Cells, and Increase in Alveolar Wall Area

“…While confirmatory and additional data are needed for definitive conclusions, the findings are in accord with prior animal studies where ambient levels of NO, and/or 0, have been shown to alter alveolar epithelial cells and alveolar walls Richter, 1982, 1986;Sherwin et al, 1983aSherwin et al, , 1985. The same kinds of alterations were found in this study on comparing mice exposed to the Los Angeles atmosphere with a matched group in Santa Barbara, that is, greater numbers of Type 2 cells (p -.05), larger Type 2 cells (total cell area per lung field as well as mean area per cell, p = .01 and p -.06, respectively), and more alveolar wall area (p < .OOl).…”

“…The investigation is an extension of earlier studies where mice had been exposed to ambient levels of nitrogen dioxide (NO,) and/or ozone (03) and lung alterations were detected, in particular increases in numbers and size of Type 2 cells and increases in the amount of alveolar wall area. Since the large volume measurements provided by image analysis were sufficiently sensitive to detect the effects of ambient levels of NO, (Sherwin and Richters, 1982;Sherwin et al, 1985) and O3 (Sherwin and Richters, 1986;Sherwin et al, 1983a), it seemed likely that the complex of air pollutants in community atmospheres would also cause detectable alterations of the lung.…”

Effect of 0.3 ppm ozone exposure on type II cells and alveolar walls of newborn mice: An image‐analysis quantitation

“…Comparable increases were found in the earlier study of the adult mouse exposed to ozone (Sherwin et al, 1983) and following NO 2 exposure of both adult and newborn mice (Sherwin and Richters, 1982;Sherwin et al, 1985). Furthermore, an 11% increase (p = 0.07) in "non-cellular interstitium" occurred when young adult rats were exposed to 0.25 ppm ozone (Barry et al, 1983).…”

“…Moreover, since ozone-induced type II cell hyperplasia tends to predominate in the proximal acinus of the lung (Boorman et al, 1980;Eustis et al, 1981;Chow et al, 1981), there has very likely been an accentuation of the masking effect-i.e., "crowding" of type II cells in a localized area facilitates cell abutment. As cited in an earlier report (Sherwin et al, 1985), type II cell hyperplasia following hyperoxia and superambient NO 2 exposure can lead to total replacement of the alveolar lining by type II cells. There are also structural differences between the newborn and adult lung that may facilitate cell abutment, in particular an incomplete expansion of alveoli in the developing lung (Thurlbeck, 1975).…”

“…Barry and her associates (1983) simultaneously reported a type II cell increase in the lungs of newborn rats following 0.25 ppm ozone exposure. We have also shown that type II cell hyperplasia occurred following exposure of both newborn and adult mice to nitrogen dioxide (Sherwin and Richters, 1982;Sherwin and Richters, 1985). Further, type II cell hyperplasia is a well-recognized finding following exposure of mammals in general to diverse noxious agents and occurs in a great variety of human lung diseases (Witschi, 1976;Watanabe et al, 1972).…”