Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs |
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Authors: | Inge Brouns Fusun Oztay Isabel Pintelon Ian De Proost Robrecht Lembrechts Jean-Pierre Timmermans Dirk Adriaensen |
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Institution: | (1) Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Groenenborgerlaan 171, 2020 Antwerp, Belgium;(2) Department of Biology, Science Faculty, Istanbul University, Vezneciler, 34134 Istanbul, Turkey |
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Abstract: | As best characterized for rats, it is clear that pulmonary neuroepithelial bodies (NEBs) are contacted by a plethora of nerve
fiber populations, suggesting that they represent an extensive group of multifunctional intraepithelial airway receptors.
Because of the importance of genetically modified mice for functional studies, and the current lack of data, the main aim
of the present study was to achieve a detailed analysis of the origin and neurochemical properties of nerve terminals associated
with NEBs in mouse lungs. Antibodies against known selective markers for sensory and motor nerve terminals in rat lungs were
used on lungs from control and vagotomized mice of two different strains, i.e., Swiss and C57-Bl6. NEB cells were visualized
by antibodies against either the general neuroendocrine marker protein gene-product 9.5 (PGP9.5) or calcitonin gene-related
peptide (CGRP). Thorough immunohistochemical examination of NEB cells showed that some of these NEB cells also exhibit calbindin
D-28 k (CB) and vesicular acetylcholine transporter (VAChT) immunoreactivity (IR). Mouse pulmonary NEBs were found to receive
intraepithelial nerve terminals of at least two different populations of myelinated vagal afferents: (1) Immunoreactive (ir)
for vesicular glutamate transporters (VGLUTs) and CB; (2) expressing P2X2 and P2X3 ATP receptors. CGRP IR was seen in varicose vagal nerve fibers and in delicate non-vagal fibers, both in close proximity
to NEBs. VAChT immunostaining showed very weak IR in the NEB-related intraepithelial vagal sensory nerve terminals. nNOS-
or VIP-ir nerve terminals could be observed at the base of pulmonary NEBs. While a single NEB can be contacted by multiple
nerve fiber populations, it was clear that none of the so far characterized nerve fiber populations contacts all pulmonary
NEBs. The present study revealed that mouse lungs harbor several populations of nerve terminals that may selectively contact
NEBs. Although at present the physiological significance of the innervation pattern of NEBs remains enigmatic, it is likely
that NEBs are receptor–effector end-organs that may host complex and/or multiple functional properties in normal airways.
The neurochemical information on the innervation of NEBs in mouse lungs gathered in the present study will be essential for
the interpretation of upcoming functional data and for the study of transgenic mice. |
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Keywords: | Sensory airway receptors Myelinated vagal afferents C-fibers ATP receptors Glutamate NEBs Airways |
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