Hyperplasia of pulmonary neuroepithelial bodies (NEB) in lungs of prolyl hydroxylase -1(PHD-1) deficient mice.
Pulmonary NEB, widely distributed within the airway mucosa of mammalian lungs, are presumed hypoxia sensitive airway O(2) 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 O(2)-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.
Department of The Paediatric Laboratory Medicine Research Institute, University of Toronto, Toronto, ON, Canada.
Jie
J
Pan
Herman
H
Yeger
Peter
P
Ratcliffe
Tammie
T
Bishop
Ernest
E
Cutz
D000818:Animals; D005455:Fluorescent Antibody Technique; D006965:Hyperplasia; D007124:Immunoenzyme Techniques; D008168:Lung / Q000201:enzymology / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D046568:Neuroepithelial Bodies / Q000473:pathology*; D011393:Procollagen-Proline Dioxygenase / Q000502:physiology*
C522721:PHD1 protein, mouse; C522722:PHD3 protein, mouse; D011393:Procollagen-Proline Dioxygenase