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Hyperplasia of Pulmonary Neuroepithelial Bodies (NEB) in Lungs of Prolyl Hydroxylase −1(PHD-1) Deficient Mice

  • Jie Pan
  • Herman Yeger
  • Peter Ratcliffe
  • Tammie Bishop
  • Ernest CutzEmail author
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 758)

Abstract

Pulmonary NEB, widely distributed within the airway mucosa of mammalian lungs, are presumed hypoxia sensitive airway O2 sensors responding to changes in airway gas concentration. NEB cell hyperplasia has been reported after exposure to chronic hypoxia and in a variety of paediatric and adult lung disorders. Prolyl hydroxylases (PHD 1–3) regulate the stability of hypoxia-inducible factors (HIF’s) in an O2-dependent manner and function as intrinsic oxygen sensors. To determine a possible role of PHD-1in NEB cells we have quantitated NEB’s in lungs of neonatal (P2) and adult (2 months) PHD-1-deficient mice and compared them to wild type (WT) control mice. Lung tissues fixed in formalin and embedded in paraffin were processed for immunoperoxidase method and frozen sections for multilabel immunoflourescence using antibodies for NEB markers synaptophysin, synaptic vesicle protein 2 and the peptide CGRP. The frequency and size of NEB in lungs of PHD-1 deficient neonatal mice (P2) and at 2 months was increased significantly compared to WT controls (p < 0.01). The present data suggests an important role for PHD enzymes in NEB cell biology deserving further studies. Since the PHD-1 deficient mouse appears to be the first animal model showing NEB cell hyperplasia it may be useful for studies of NEB physiology and pathobiology.

Keywords

Airway oxygen sensors Neuroendocrine cells Oxygen sensing mechanism Cell proliferation and differentiation Prolyl hydroxylases Hypoxia-inducible factor -1 

Notes

Acknowledgements

Supported by grants from the Canadian Institutes for Health Research (MOP 15270) and Canadian Cystic Fibrosis to E.C. and H.Y and Wellcome Trust (Programme grant #091857 ) to P.R. and T.B.

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Copyright information

© Springer Science+Business Media Dordrecht 2012

Authors and Affiliations

  • Jie Pan
    • 1
  • Herman Yeger
    • 1
  • Peter Ratcliffe
    • 2
  • Tammie Bishop
    • 2
  • Ernest Cutz
    • 3
    Email author
  1. 1.Division of Pathology, Department of The Paediatric Laboratory Medicine Research Institute, The Hospital for Sick Children, and Department of Laboratory Medicine and PathobiologyUniversity of TorontoTorontoCanada
  2. 2.The Henry Wellcome Building for Molecular PhysiologyUniversity of OxfordOxfordUK
  3. 3.Division of Pathology, Department of Pediatric Laboratory MedicineThe Research Institute, The Hospital for Sick ChildrenTorontoCanada

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