Cell proliferation contributes to pulmonary neuroendocrine cell
hyperplasia following acute airway injury.
Stevens, Timothy P., John T. McBride, Janice L. Peake, Kent E.
Pinkerton, Barry R. Stripp.
Departments of Pediatrics and Environmental Medicine, School of
Medicine and Dentistry, University of Rochester, Rochester NY, USA,
_Department of Anatomy, School of Veterinary Medicine, University of
California, Davis, Davis California, USA
APStracts 3:0223L, 1996.
Pulmonary neuroendocrine cells (PNECs) are airway epithelial cells
capable of secreting a variety of neuropeptides. PNECs are scattered
throughout the bronchial tree either as individual cells or clusters
of cells called neuroepithelial bodies (NEBs). PNECs and their
secretory peptides have been considered to play a role in fetal lung
development. Although the normal physiologic function of PNECs and
neuropeptides in normal adult lungs and in repair from lung injury is
not known, 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 changes in PNEC number and distribution following acute
airway injury, FVB/n mice were treated with either naphthalene or
vehicle. Naphthalene is an aromatic hydrocarbon which, at the dose
used in this study, selectively destroys non-ciliated bronchial
epithelial cells (Clara cells) through cytochrome P450 mediated
metabolic activation into cytotoxic epoxides. PNECs were identified
by immunohistochemical analysis of CGRP-like immunoreactivity (CGRP
-IR). Proliferating cells were marked with 3H thymidine incorporation.
Acute naphthalene toxicity results in PNEC hyperplasia detectable
after 5 days recovery. PNEC hyperplasia is characterized by increased
numbers of NEBs without significant changes in the number of isolated
PNECs and by increased 3H thymidine labelling of CGRP-IR cells. These
data show that cell proliferation contributes to PNEC hyperplasia
following acute airway injury and suggest that PNECs may be capable
of more rapidly increasing their number in response to injury than
previously recognized.
Received 19 July 1996; accepted in final form 28 October 1996.
APS Manuscript Number L229-6.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996