CELL-PROLIFERATION CONTRIBUTES TO PNEC HYPERPLASIA AFTER ACUTE AIRWAYINJURY

Pulmonary neuroendocrine cells (PNECs) are airway epithelial cells tha t are capable of secreting a variety of neuropeptides. PNECs are scatt ered throughout the bronchial tree either as individual cells or clust ers of cells termed neuroepithelial bodies (NEBs). PNECs and their sec retory peptides have been considered to play a role in fetal lung deve lopment. Although the normal physiological function of PNECs and neuro peptides in normal adult lungs and in repair from lung injury is not k nown, PNEC hyperplasia has been associated with chronic lung diseases, such as bronchopulmonary dysplasia, and with chronic exposures, such as hypoxia, tobacco smoke, nitrosamines, and ozone. To evaluate change s in PNEC number and distribution after acute airway injury, FVB/n mic e were treated with either naphthalene or vehicle. Naphthalene is an a romatic hydrocarbon that, at the dose used in this study, selectively destroys nonciliated bronchial epithelial cells (Clara cells) through cytochrome P-450-mediated metabolic activation into cytotoxic epoxides . PNECs were identified by immunohistochemical analysis of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Proliferating ce lls were marked with [H-3]thymidine incorporation. Acute naphthalene t oxicity results in PNEC hyperplasia that is detectable after 5 days of recovery. PNEC hyperplasia is characterized by increased numbers of N EBs without significant changes in the number of isolated PNECs and by increased [H-3]thymidine labeling of CGRP-IR cells. These data show t hat cell proliferation contributes to PNEC hyperplasia after acute air way injury and suggest that PNECs may be capable of more rapidly incre asing their number in response to injury than previously recognized.