Comparative histology of pulmonary neuroendocrine cell system in mammalian lungs

Abstract

It is increasingly recognized that neuroepithelial endocrine cells and organoid clusters of these cells termed neuroepithelial bodies are widely distributed in the respiratory tract of vertebrates. This review focuses on the neuroepithelial endocrine system in the airway epithelium of mammals according to observations made in a wide range of species, as it appears in light and electron microscopy by means of various visualization techniques under normal and experimental conditions. Because there are similarities but also marked differences between species, wherever possible studies in human airways are emphasized. Conventional histochemical and ultrastructural studies including microspectrofluorimetry have demonstrated the amine‐handling properties and the presence of neurosecretory granules in neuroendocrine cells of the epithelium of all mammals studied so far. The neuroepithelial bodies are innervated by morphological afferent‐ and efferentlike synaptic specializations. These, together with the presence of reciprocal synapses, emphasize that these cells may be involved in dual functions of chemoreception and secretion. Light and electron microscopic immunohistochemistry has demonstrated that neuroepithelial endocrine cells may contain various biogenic agents, suggesting that the neuroendocrine system is highly heterogeneous. Neural elements may interact in a complex manner, and the activation of certain neural pathways may control the release of biogenic substances to influence physiological airway functions. They may be particularly relevant in pulmonary diseases. Consequently, the function of this system is complex and it is highly probable that many of its aspects are still not elucidated. Microsc. Res. Tech. 37:31–42, 1997. © 1997 Wiley‐Liss, Inc.

Mechanical stretch-induced serotonin release from pulmonary neuroendocrine cells: implications for lung development

“…Hypoxia induced 5-HT release from NEB cells is dose dependent and occurs within the physiological range expected in the airway (PO 2 ϳ 95 mmHg) (17). The precise role of solitary PNEC and whether they are functionally distinct from NEB is not known, although they share identical neuroendocrine and molecular markers as well as innervation (13,34,40). PNEC/NEB appear prominent in fetal and neonatal lungs but are less conspicuous in the lungs of adults because of a "dilutional" effect of postnatal lung growth (20).…”

“…We conclude that mechanical strain is an important physiological stimulus for the release of 5-HT from PNEC via mechanosensitive channels with potential effects on lung development and resorption of lung fluid at the time of birth. mechanosensitive ion channels; amine storage pools; neuroendocrine cell secretion; hypoxia-induced secretion; fetal lung fluid THE SYSTEM OF PULMONARY NEUROENDOCRINE CELLS (PNEC) is composed of amine (serotonin, 5-HT)-and peptide (e.g., bombesin, calcitonin)-producing cells widely distributed within the airway mucosa of human and animal lungs (13,34,40). PNEC occur as single cells and as distinctive innervated clusters, neuroepithelial bodies (NEB).…”

“…In addition, two morphological types of PNEC have been recognized in human fetal lungs, one having a flask shape with apical cytoplasmic processes reaching the airway lumen, or the so-called "open type," and PNEC with elongated dendritic-like cytoplasmic processes extending along the basement membrane without a luminal contact ("closed type") (13,34,40). The PNEC type with dendritic cytoplasmic processes is found only in fetal or neonatal lungs (39).…”

Hyperplasia of Alveolar Neuroendocrine Cells in Rat Lung Carcinogenesis by Silica with Selective Expression of Proadrenomedullin-Derived Peptides and Amidating Enzymes

“…Several other immunohistochemical markers label these cells: neuron-specific enolase, chromogranin, PGP 9.5, serotonin, etc. (Scheuermann, 1997). There is a considerable interspecies variation in the pattern of peptides expressed by pulmonary NE cells, but in the three species that we studied (rat, hamster, and mouse) CGRP is the most abundant peptide (Van Lommel et al, 1995) and can be used as a general marker for the endocrine population of the lung.…”

Pulmonary Neuroendocrine Cell-Secreted Factors May Alter Fetal Lung Liquid Clearance

“…They secrete many mediators, including dopamine (DA), serotonin, gastrin-releasing peptide (GRP), and somatostatin, (7)(8)(9) which may play a role in the lungs' transition to postnatal life by altering fetal lung epithelial ion and fluid transport. DA concentrations are maximal at birth (10), and it is known to alter alveolar fluid transport by increasing Na ϩ channel and Na ϩ /K ϩ -ATPase activity (10,11).…”