Evidence for a role of neuroepithelial bodies as complex airway sensors: comparison with smooth muscle-associated airway receptors

Abstract

The epithelium of intrapulmonary airways in many species harbors diffusely spread innervated groups of neuroendocrine cells, called neuroepithelial bodies (NEBs). Data on the location, morphology, and chemical coding of NEBs in mammalian lungs are abundant, but none of the proposed functions has so far been fully established. Besides C-fiber afferents, slowly adapting stretch receptors, and rapidly adapting stretch receptors, recent reviews have added NEBs to the list of presumed sensory receptors in intrapulmonary airways. Physiologically, the innervation of NEBs, however, remains enigmatic. This short overview summarizes our present understanding of the chemical coding and exact location of the receptor end organs of myelinated vagal airway afferents in intrapulmonary airways. The profuse populations that selectively contact complex pulmonary NEB receptors are compared with the much smaller group of smooth muscle-associated airway receptors. The main objective of our contribution was to stimulate the idea that the different populations of myelinated vagal afferents that selectively innervate intraepithelial pulmonary NEBs may represent subpopulations of the extensive group of known electrophysiologically characterized myelinated vagal airway receptors. Future efforts should be directed toward finding out which airway receptor groups are selectively coupled to the complex NEB receptors.

Bronchopulmonary neuroendocrine tumors

“…3). 16 Although most PNEC exist as solitary cells, some are aggregated in innervated PNEC clusters referred to as neuroepithelial bodies (NEBs). 17 Both solitary PNECs and NEB exhibit similar phenotypes in terms of storage of adenosine triphosphate, serotonin (5-HT), and several other amines and neuropeptides in dense-core vesicles.…”

Neuro-immune interactions during development of pulmonary fibrosis

“…They may aggregate to form NEBs, which are innervated by vagal, spinal, and parabronchial nerves [18]. NEBs are connected to the central nervous system via the sympathetic nerve and nociceptors (C fiber receptors and high threshold A delta fiber receptors) in the vagus nerve [19].…”

“…NEBs are connected to the central nervous system via the sympathetic nerve and nociceptors (C fiber receptors and high threshold A delta fiber receptors) in the vagus nerve [19]. In addition, NEBs are in direct contact with sensory afferents that immunereactive for substance P (SP) [18] and may cause neurogenic airway inflammation [19]. PNECs/NEBs can release many bioactive substances with growth factors and mitogenic properties, such as bombesin/ Gastrin-Releasing Peptide (GRP), Calcitonin Gene-Related Peptide (CGRP), and 5-hydroxytryptamine (5-HT) [20].…”

Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells

“…Their location as an integrated component of the epithelial lining of intrapulmonary airways in all air-breathing vertebrate groups, makes them ideally placed to sense changes in the airway environment and transduce this information to the central nervous system Adriaensen et al, 2006;Brouns et al, 2009b;Brouns et al, 2012). The characteristics of the excitable NEB cells clearly allow the perception of environmental stimuli.…”

“…The involvement of NEBs in postnatal mechanosensing has recently regained interest (Lembrechts et al, 2011;Lembrechts et al, 2012). Postnatally, the close association of NEB cells with afferent nerve terminals argues for a function as a sensory receptor (Adriaensen et al, 2006), although the exact stimuli and molecular transduction mechanisms that are involved in their activation remain a matter of debate.…”