Functional implications of extensive new data on the innervation of pulmonary neuroepithelial bodies

Pulmonary neuroepithelial bodies (NEBs) are innervated organoid groups of neuroendocrine cells, present in the epithelial lining of intrapulmonary airways of man and all air-breathing vertebrates studied so far. NEBs receive a vagal nodose sensory innervation that is considered by other authors as their main, if not their only innervation, although apparently not needed for the normal development and maintenance of NEBs. In the present study of NEBs in the developing rat lung (gestational day 16 - adult), immunoreactivity (IR) for calcitonin gene-related peptide (CGRP; a marker for NEBs), protein gene product 9.5 (PGP9.5; a marker for NEBs and neuronal elements), calbindin D28k (CB; a calcium binding protein), and for the growth-associated protein 43 (GAP-43; a marker for growing or remodelling nerve fibers) was combined with vagal denervation experiments. GAP-43 and CB IR revealed that the vagal sensory innervation of airways precedes the prenatal development of NEBs by several generations of branching. Unlike several other nerve fiber populations innervating NEBs, the vagal sensory component apparently does not express GAP-43 IR in mature lungs. GAP-43 labelling, however, did reveal newly ingrowing intraepithelial vagal sensory fibers, specifically reinnervating NEBs in adult rats 2 weeks following a cervical vagal crush. In conclusion, details of the innervation of pulmonary NEBs were disclosed that had been invisible so far, shedding new light on its complexity and probable involvement in the normal development and functional maintenance of NEBs throughout life.