Type II cell proliferation related to migration of inflammatory cells into the lung.

Enhanced proliferation of epithelial cells in the lung is usually associated with some form of cellular injury. However, increased epithelial cell proliferation has also been observed in the absence of morphological signs of cellular injury. The nature of the stimuli to cell proliferation in the absence of cell injury is not clear. We hypothesized that one stimulus to epithelial cell proliferation in the absence of morphological injury to lung cells was the migration of inflammatory cells through the epithelium from the vasculature. This hypothesis was tested by comparing proliferation in the lungs of normal mice with that of white blood cell (WBC)-depleted mice when migration of WBC was stimulated by carbon instillation. White blood cell depletion in mice was accomplished with injections of 89SrCl2 (irradiated group). Sixteen days later, when WBC levels were reduced by about 64%, 4 mg colloidal carbon was instilled intratracheally into both normal and irradiated mice. At intervals of 1 through 4, 7, and 14 days after carbon instillation, four mice in each group were given ip tritiated thymidine and killed 1 hr later, and the lungs lavaged and prepared for electron microscopy and light microscope autoradiography. Analysis of lavage fluid revealed about 69% fewer cells in the irradiated mice compared to the normal mice at 1 day. There was no electron microscopic evidence of injury to the alveolar epithelium in either the normal or irradiated mice but there was increased proliferation of Type II cells. The proliferative response of Type II cells was 100 and 300% greater in the normal lung compared to irradiated mice at 3 and 4 days after carbon instillation, respectively. These data support the hypothesis that epithelial cell proliferation in the lung, in the absence of cellular injury, is related to the migration of WBC into the lung.