Premium
Increased neuropeptide Y innervation in the airway epithelium of mice overexpressing Nerve Growth Factor
Author(s) -
Dey Richard D,
Batchelor Thomas P,
Hoyle Gary W
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.1009.11
Subject(s) - nerve growth factor , neuropeptide y receptor , medicine , endocrinology , neuropeptide , biology , neurotrophin , epithelium , immunocytochemistry , genetically modified mouse , respiratory epithelium , axon , transgene , microbiology and biotechnology , respiratory system , receptor , biochemistry , genetics , gene
The neurotrophin, nerve growth factor (NGF), supports nerve growth and axon sprouting of sensory and sympathetic neurons. NGF is elevated in asthmatics and contributes to airway hyperresponsiveness and inflammation. Overexpression of NGF has been reported in lungs of transgenic mice by linking the NGF gene to the Clara cell secretory protein (CCSP) promoter. These mice overexpress catecholamines and the neuropeptide substance P. Since sympathetic nerves respond to NGF, we hypothesized that NPY might be elevated in the NGF‐CCSP mice. NGF‐CCSP and wild‐type mice were prepared for quantitative immunocytochemistry for neuropeptide Y (NPY) and the pan‐neuronal marker PGP 9.5. Nerve fiber density (NFD) of NPY (n=3) in epithelium of the NGF‐CCSP transgenic mice (1.28 + 0.26%) was significantly increased compared to the epithelium of wild‐type mice (0.09 + 0.012%). PGP 9.5 NFD (n=1) in the transgenic mice was also increased (2.86 %) compared to wild‐type (0.07%). These findings support two important conclusions. First, that NGF overexpression substantially enhances NPY innervation of airway epithelium, which is normally very low. Second, the increased PGP 9.5 innervation indicates that NGF‐induced nerve fiber sprouting and growth had occurred within the epithelium. The findings suggest that increased NGF release known to occur during development or environmental exposures may control airway epithelial innervation. Funded by NIH HL35812 and HL80566.