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CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia.

Publication ,  Journal Article
Willett, CG; Shahsafei, A; Graham, SA; Sunday, ME
Published in: Am J Respir Cell Mol Biol
July 1999

In previous studies, we demonstrated that pulmonary neuroendocrine cell (PNEC) hyperplasia in hamsters treated with diethylnitrosamine (DEN) plus 65% hyperoxia (DEN/O2) reflects predominantly neuroendocrine cell differentiation. Several peptides implicated in non-neoplastic PNEC hyperplasia are hydrolyzed by CD10/neutral endopeptidase 24.11 (CD10/NEP), an enzyme known to downregulate neurogenic inflammation of the lung by modulating locally effective concentrations of multiple bioactive peptides. In fetal mice, we observed that CD10/NEP inhibition by SCH32615 potentiates cell proliferation and type II cell differentiation in the lung in utero. Further, CD10/NEP messenger RNA levels parallelled relative PNEC numbers in DEN/O2-treated hamster lung, suggesting that the enzyme might mediate spontaneous regression of PNEC hyperplasia. The goals of the present study were: (1) to determine whether CD10/NEP inhibition would alter the extent of PNEC hyperplasia occurring in these hamsters, and (2) to analyze cellular mechanisms potentially involved in altering numbers of PNECs in this model. We administered SCH32615 chronically to a subset of DEN/O2-treated hamsters. Immunostaining of lungs from the CD10/ NEP-inhibited subset demonstrated significant acceleration of the development of PNEC hyperplasia, increased PNEC proliferation, and diminished PNEC apoptosis as compared with animals receiving no SCH32615. These observations indicate that PNEC hyperplasia can occur as a result of multiple cellular processes, including increased neuroendocrine cell differentiation, proliferation, and survival. CD10/NEP modulates PNEC numbers primarily by promoting cell differentiation and proliferation during lung injury, probably via increasing the half-life of bioactive peptides in the lung.

Duke Scholars

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

July 1999

Volume

21

Issue

1

Start / End Page

13 / 20

Location

United States

Related Subject Headings

  • Time Factors
  • Respiratory System
  • Protease Inhibitors
  • Proliferating Cell Nuclear Antigen
  • Oxygen
  • Neurosecretory Systems
  • Neprilysin
  • Lung
  • In Situ Nick-End Labeling
  • Immunoenzyme Techniques
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Willett, C. G., Shahsafei, A., Graham, S. A., & Sunday, M. E. (1999). CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia. Am J Respir Cell Mol Biol, 21(1), 13–20. https://doi.org/10.1165/ajrcmb.21.1.3389
Willett, C. G., A. Shahsafei, S. A. Graham, and M. E. Sunday. “CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia.Am J Respir Cell Mol Biol 21, no. 1 (July 1999): 13–20. https://doi.org/10.1165/ajrcmb.21.1.3389.
Willett CG, Shahsafei A, Graham SA, Sunday ME. CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia. Am J Respir Cell Mol Biol. 1999 Jul;21(1):13–20.
Willett, C. G., et al. “CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia.Am J Respir Cell Mol Biol, vol. 21, no. 1, July 1999, pp. 13–20. Pubmed, doi:10.1165/ajrcmb.21.1.3389.
Willett CG, Shahsafei A, Graham SA, Sunday ME. CD10/neutral endopeptidase inhibition augments pulmonary neuroendocrine cell hyperplasia in hamsters treated with diethylnitrosamine and hyperoxia. Am J Respir Cell Mol Biol. 1999 Jul;21(1):13–20.

Published In

Am J Respir Cell Mol Biol

DOI

ISSN

1044-1549

Publication Date

July 1999

Volume

21

Issue

1

Start / End Page

13 / 20

Location

United States

Related Subject Headings

  • Time Factors
  • Respiratory System
  • Protease Inhibitors
  • Proliferating Cell Nuclear Antigen
  • Oxygen
  • Neurosecretory Systems
  • Neprilysin
  • Lung
  • In Situ Nick-End Labeling
  • Immunoenzyme Techniques