Comparative histology of pulmonary neuroendocrine cell system in mammalian lungs

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 studies 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.