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PMID: 12107102 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Terminal bronchioles harbor a unique airway stem cell population that localizes to the bronchoalveolar duct junction.

The American journal of pathology ·Vol. 161 ·No. 1 ·2002-07-00 ·Pages 173-82

Giangreco A, Reynolds SD, Stripp BR

Abstract

Cellular mechanisms contributing to renewal of terminal bronchioles remain poorly defined. Our previous studies identified pollutant-resistant Clara cell secretory protein (CCSP)-expressing stem cells that localize to the neuroepithelial body (NEB) and contribute to renewal of the proximal bronchiolar epithelium. However, activation of NEB-associated stem cells is unlikely to contribute to renewal of terminal bronchiolar epithelium because of the paucity of NEBs at this location. Goals of this study were to determine the location and properties of cells contributing to renewal of terminal bronchioles after Clara cell depletion. Pollutant-resistant CCSP-expressing cells were identified that localized to the bronchoalveolar duct junction (BADJ) and contribute to restoration of a phenotypically diverse epithelium. CCSP-expressing cells comprise the predominant proliferative population in initial terminal bronchiolar repair and include a population of label-retaining cells suggesting that they maintain characteristics of a stem cell population. Furthermore, immunohistochemical co-localization studies involving CCSP and the NEB-specific marker calcitonin gene-related peptide indicate that BADJ-associated CCSP-expressing stem cells function independently of NEB microenvironments. These studies identify a BADJ-associated, NEB-independent, CCSP-expressing stem cell population in terminal bronchioles and support the notion that regiospecific stem cell niches function to maintain epithelial diversity after injury.

MeSH Terms
Animals Bronchi/cytology,drug effects,pathology,physiology Calcitonin Gene-Related Peptide/metabolism Cell Cycle/physiology Cell Division Drug Resistance Male Mice Mice, Inbred Strains Naphthalenes/pharmacology Neurosecretory Systems/cytology,metabolism Proteins/drug effects,genetics,metabolism Pulmonary Alveoli/cytology RNA, Messenger/metabolism Regeneration/physiology Respiratory Mucosa/cytology Respiratory Physiological Phenomena Stem Cells/cytology Uteroglobin
Chemicals
Naphthalenes Proteins RNA, Messenger Scgb1a1 protein, mouse naphthalene Uteroglobin Calcitonin Gene-Related Peptide
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Giangreco Adam
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.
Reynolds Susan D
Stripp Barry R
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Article Info
Journal
The American journal of pathology
Abbr.
Am J Pathol
ISSN
0002-9440
DOI
10.1016/S0002-9440(10)64169-7
Published
2002-07-00
Pages
173-82
Language
English
Region
United States
NLM ID
0370502
PMCID
PMC1850682
Subset
IM
Grants
NHLBI NIH HHS · R01 HL070575 · United States
NHLBI NIH HHS · HL70575 · United States
NIEHS NIH HHS · ES07026 · United States
NIEHS NIH HHS · R01 ES007026 · United States
NIEHS NIH HHS · R01 ES008964 · United States
NIEHS NIH HHS · ES08964 · United States
NHLBI NIH HHS · R01 HL064888 · United States
NIEHS NIH HHS · T32 ES007026 · United States
NHLBI NIH HHS · HL64888 · United States
External Links
PubMed source DOI: 10.1016/S0002-9440(10)64169-7 PMC Full Text View journal details
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