Clara cell secretory protein-expressing cells of the airway neuroepithelial body microenvironment include a label-retaining subset and are critical for epithelial renewal after progenitor cell depletion.

Published

Journal Article

Stem cells with potential to contribute to the re-establishment of the normal bronchiolar epithelium have not been definitively demonstrated. We previously established that neuroepithelial bodies (NEBs) sequester regenerative cells that contribute to bronchiolar regeneration after selective chemical depletion of Clara cells, a major progenitor cell population. Two candidate stem cells were identified on the basis of proliferative potential after chemical ablation: a pollutant-resistant subpopulation of Clara cells that retain their expression of Clara cell secretory protein (CCSP) (variant CCSP-expressing [CE] cells or vCE cells) and calcitonin gene-related peptide (CGRP)-expressing pulmonary neuroendocrine cells (PNECs). In the present study, two populations of label-retaining cells were identified within the NEB: CGRP-expressing cells and a subpopulation of CE cells. To investigate contributions made by CE and CGRP-expressing cells to epithelial renewal, CE cells were ablated through acute administration of ganciclovir to transgenic mice expressing herpes simplex virus thymidine kinase under the regulatory control of the mouse CCSP promoter. CGRP-immunoreactive PNECs proliferated after depletion of CE cells, yet were unable to repopulate CE cell-depleted airways. These results support the notion that vCE cells represent either an airway stem cell or are critical for stem cell maintenance, and suggest that PNECs are not sufficient for epithelial renewal.

Full Text

Duke Authors

Cited Authors

  • Hong, KU; Reynolds, SD; Giangreco, A; Hurley, CM; Stripp, BR

Published Date

  • June 2001

Published In

Volume / Issue

  • 24 / 6

Start / End Page

  • 671 - 681

PubMed ID

  • 11415931

Pubmed Central ID

  • 11415931

Electronic International Standard Serial Number (EISSN)

  • 1535-4989

International Standard Serial Number (ISSN)

  • 1044-1549

Digital Object Identifier (DOI)

  • 10.1165/ajrcmb.24.6.4498

Language

  • eng