Progression of type II cell hypertrophy and hyperplasia during silica-induced pulmonary inflammation.

Type II cell hyperplasia and hypertrophy were quantitated in the lungs of rats exposed to silica by using intratracheal injection. Hypertrophic type II cells were separated from normal type II cells by means of centrifugal elutriation of cells dispersed from the lungs by using protease. Type II cell hypertrophy was also quantitated, in situ, by measuring cell profile areas in lung sections. As a means of distinguishing between the hyperplastic and hypertrophic responses of type II cells we followed the progression of these two responses as a function of time and of dose. Seven, 14, and 28 days after a single intratracheal injection of silica (10 mg/rat), hypertrophic type II cells accounted for 33, 35, and 57% of the total type II cells recovered from the lungs. In contrast, hypertrophic type II cells accounted for less than 15% of the type II cells from control lungs. The appearance of hypertrophic type II cells was dose-related when examined 2 weeks after dosing; however, after only 1 week, the response of the type II cell appeared independent of dose. The hypertrophic response of type II cells could not be separated from the hyperplastic response according to either dose or time responses. These data support the hypothesis that in the lungs of silica-treated rats, the hypertrophic type II cell may be the proliferative type II cell. In addition, the hypertrophic type II cell appears to underlie the marked increases in surfactant levels seen in silica-treated lungs.