Cell proliferation contributes to PNEC hyperplasia after acute airway injury

Timothy P. Stevens, John T. Mcbride, Janice L. Peake, Kent E Pinkerton, Barry R. Stripp

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Pulmonary neuroendocrine cells (PNECs) are airway epithelial cells that are capable of secreting a variety of neuropeptides. PNECs are scattered throughout the bronchial tree either as individual cells or clusters of cells termed neuroepithelial bodies (NEBs). PNECs and their secretory peptides have been considered to play a role in fetal lung development. Although the normal physiological 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 after acute airway injury, FVB/n mice were treated with either naphthalene or vehicle. Naphthalene is an aromatic 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 cells were marked with [3H]thymidine incorporation. Acute naphthalene toxicity results in PNEC hyperplasia that is detectable after 5 days of recovery. PNEC hyperplasia is characterized by increased numbers of NEBs without significant changes in the number of isolated PNECs and by increased [3H]thymidine labeling of CGRP-IR cells. These data show that cell proliferation contributes to PNEC hyperplasia after acute airway injury and suggest that PNECs may be capable of more rapidly increasing their number in response to injury than previously recognized.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume272
Issue number3 16-3
StatePublished - Mar 1997
Externally publishedYes

Fingerprint

Neuroendocrine Cells
Hyperplasia
Cell Proliferation
Lung
Wounds and Injuries
Neuroepithelial Bodies
Calcitonin Gene-Related Peptide
Lung Injury
Neuropeptides
Thymidine
Epithelial Cells
Aromatic Hydrocarbons
Bronchopulmonary Dysplasia
Nitrosamines
Ozone
Epoxy Compounds
Fetal Development
Smoke
Cytochrome P-450 Enzyme System
Lung Diseases

Keywords

  • calcitonin gene-related peptide
  • lung
  • naphthalene
  • neuroepithelial body
  • pulmonary neuroendocrine cells

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Cell proliferation contributes to PNEC hyperplasia after acute airway injury. / Stevens, Timothy P.; Mcbride, John T.; Peake, Janice L.; Pinkerton, Kent E; Stripp, Barry R.

In: American Journal of Physiology - Lung Cellular and Molecular Physiology, Vol. 272, No. 3 16-3, 03.1997.

Research output: Contribution to journalArticle

Stevens, Timothy P. ; Mcbride, John T. ; Peake, Janice L. ; Pinkerton, Kent E ; Stripp, Barry R. / Cell proliferation contributes to PNEC hyperplasia after acute airway injury. In: American Journal of Physiology - Lung Cellular and Molecular Physiology. 1997 ; Vol. 272, No. 3 16-3.
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