The pulmonary neuroendocrine system consists of specialized airway endocrine epithelial cells, associated with nerve fibres. The epithelial cells, the pulmonary neuroendocrine cells (PNEC), can be solitary or clustered to form neuroepithelial bodies (NEB). During the last thirty years, the pulmonary neuroendocrine system has been intensively investigated and much knowledge of its function has been obtained. This text reviews work which dates from the last ten years. In this period, the picture of the pulmonary neuroendocrine system we previously had, has not fundamentally changed. The pulmonary neuroendocrine system is still regarded as an oxygen sensitive chemoreceptor with local and reflex-mediated regulatory functions, and as a regulator of airway growth and development. Continuing research has much more refined this picture. This text reviews several aspects of the pulmonary neuroendocrine system: phylogeny, the amine and peptide content of its epithelial cells, ontogeny and influence on lung development, the influence of hypoxia and nonhypoxic stimuli, immunomodulatory function, innervation and pathology. Among the discoveries of the past decade, three stand out prominently because of their great significance: additional proof that the neural component of the pulmonary neuroendocrine system is sensory, sound experimental evidence that PNEC stimulate airway epithelial cell differentiation and the discovery of a specific membrane oxygen receptor in the PNEC.
The intrapulmonary airways contain oxygen-sensitive chemoreceptors which may be analogous to the arterial chemoreceptors: the neuroepithelial bodies (NEB). While the NEB are prominent in the neonatal lung, physiological studies indicate that the carotid bodies are still relatively inactive at birth. This points to an unequal degree of development of both during the early neonatal period. As a reflexogenic chemoreceptor function depends on a well-developed innervation, we undertook a comparative investigation of the development of the NEB and the carotid body glomus cell innervation. Two morphological aspects of the innervation of NEB and carotid body glomus cells were quantified in rabbits of different age groups. The total sectional area of intracorpuscular and intraglomerular nerve endings per NEB or glomus cell group, respectively, was measured and the area percentage of mitochondria and synaptic vesicles was determined. In the NEB, no significant difference in total sectional area of the nerve endings between the age groups was observed, while in the carotid body there was a significant increase in the adult age group. In addition, the area percentage of mitochondria and synaptic vesicles of the nerve endings did not change significantly with age in the NEB, while in the carotid body these increased and decreased, respectively, with age. These observations point to a shift from morphologically efferent nerve endings, rich in synaptic vesicles, to morphologically afferent nerve endings, rich in mitochondria. Our interpretation of these findings is that, at birth, the NEB innervation is more mature than the carotid body glomus cell innervation and that the latter matures at a later time than the former. These findings support the theory that the NEB may act as complementary chemoreceptors to the carotid body during the early postnatal period.
The number and volume of pulmonary neuroepithelial bodies (NEBs) of 1- and 4-week-old hamsters were estimated using unbiased stereological principles and systematic sampling techniques. For comparative purposes, volume estimations were also made in the carotid body, the parathyroid gland, and the adrenal medulla. A significant decrease was found in the total number of NEBs, immunoreactive for CGRP, between 1 and 4 weeks. Individual as well as cumulative NEB volume also decreased significantly. The cumulative NEB volume in 1-week-old hamsters was in the same range as the volumes of the carotids and parathyroids in the same animals. The postnatal decrease of the NEB number suggests that the NEBs are of primary potential importance in the neonatal stage, when they may complement the chemoreceptor function of the carotid bodies, which are relatively inactive at birth. Since the cumulative NEB volume (at least at the age of 1 week) is equal to that of the carotid bodies and the parathyroids, their physiological function may be of similar importance.
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