Article

Functional morphology of pulmonary neuroepithelial bodies: extremely complex airway receptors.

Department of Biomedical Sciences, University of Antwerp-RUCA, Antwerp, Belgium.
The Anatomical Record Part A Discoveries in Molecular Cellular and Evolutionary Biology 02/2003; 270(1):25-40. DOI:10.1002/ar.a.10007 pp.25-40
Source: PubMed

ABSTRACT Innervated groups of neuroendocrine cells, called neuroepithelial bodies (NEBs), are diffusely spread in the epithelium of intrapulmonary airways in many species. Our present understanding of the morphology of NEBs in mammalian lungs is comprehensive, but none of the proposed functional hypotheses have been proven conclusively. In recent reviews on airway innervation, NEBs have been added to the list of presumed physiological lung receptors. Microscopic data on the innervation of NEBs, however, have given rise to conflicting interpretations. Using neuronal tracing, denervation, and immunostaining, we recently demonstrated that the innervation of NEBs is much more complex than the almost unique vagal nodose sensory innervation suggested by other authors. The aim of the present work is to summarize our present understanding about the origin and chemical coding of the profuse nerve terminals that selectively contact pulmonary NEBs. A thorough knowledge of the complex interactions between the neuroendocrine cells and at least five different nerve fiber populations is essential for defining the position(s) of NEBs among the many pulmonary receptors characterized by lung physiologists.

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    Article: A confocal microscopic study of solitary pulmonary neuroendocrine cells in human airway epithelium.
    Markus Weichselbaum, Malcolm P Sparrow, Elisha J Hamilton, Philip J Thompson, Darryl A Knight
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    ABSTRACT: Pulmonary neuroendocrine cells (PNEC) are specialized epithelial cells that are thought to play important roles in lung development and airway function. PNEC occur either singly or in clusters called neuroepithelial bodies. Our aim was to characterize the three dimensional morphology of PNEC, their distribution, and their relationship to the epithelial nerves in whole mounts of adult human bronchi using confocal microscopy. Bronchi were resected from non-diseased portions of a lobe of human lung obtained from 8 thoracotomy patients (Table 1) undergoing surgery for the removal of lung tumors. Whole mounts were stained with antibodies to reveal all nerves (PGP 9.5), sensory nerves (calcitonin gene related peptide, CGRP), and PNEC (PGP 9.5, CGRP and gastrin releasing peptide, GRP). The analysis and rendition of the resulting three-dimensional data sets, including side-projections, was performed using NIH-Image software. Images were colorized and super-imposed using Adobe Photoshop. PNEC were abundant but not homogenously distributed within the epithelium, with densities ranging from 65/mm2 to denser patches of 250/mm2, depending on the individual wholemount. Rotation of 3-D images revealed a complex morphology; flask-like with the cell body near the basement membrane and a thick stem extending to the lumen. Long processes issued laterally from its base, some lumenal and others with feet-like processes. Calcitonin gene-related peptide (CGRP) was present in about 20% of PNEC, mainly in the processes. CGRP-positive nerves were sparse, with some associated with the apical part of the PNEC. Our 3D-data demonstrates that PNEC are numerous and exhibit a heterogeneous peptide content suggesting an active and diverse PNEC population.
    Respiratory research 02/2005; 6:115. · 3.36 Impact Factor
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    Article: Pulmonary Neuroendocrine Cell System in Health and Disease
    Ernest Cutz, Herman Yeger, Jie Pan, Takaaki Ito
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    ABSTRACT: Pulmonary neuroendocrine cell (PNEC) system consists of solitary cells and innervated clusters, neuroepithe-lial bodies (NEB), widely distributed throughout the airway mucosa of mammalian lungs. These cells are numerous in fe-tal/neonatal lungs and produce amine (serotonin, 5-HT) as well as a variety of neuropeptides (e.g. bombesin). The poten-tial role and significance of these highly specialized lung cells in normal and diseased lung is only now beginning to be appreciated. The multifaceted role(s) of PNEC system include lung development, neonatal adaptation and during postnatal airway homeostasis as guardians of stem cell niche. Recent advances in cellular and molecular biology of PNEC system particularly their ontogeny and mechanisms of neuroendocrine differentiation in developing lung are reviewed. The evidence for the role of NEB as hypoxia-sensitive airway chemoreceptors is presented including identification and characterization of O2 sensor molecular complex that is activated by hypoxia leading to release of amine and peptide me-diators acting locally or via NEB neural connections. Thus NEB are postulated to function as O2 sensitive airway sensors involved in respiratory control, especially during adaptation to extrauterine life. Hyperplasia of PNEC/NEB cells, suggest-ing altered function, has been identified in a number of perinatal/pediatric lung disorders including bronchopulmonary dysplasia, central hypoventilation syndrome, Sudden Infant Death Syndrome and Neuroendocrine Hyperplasia of Infancy as well as Cystic Fibrosis and pediatric asthma. In the adults, PNEC/NEB may be involved in the pathogenesis of tobacco induced airway disease, pulmonary fibrosis and lung carcinogenesis.
    Current Respiratory Medicine Reviews 01/2008; 4:174-186.
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Keywords

airway innervation
 
chemical coding
 
complex interactions
 
conflicting interpretations
 
defining
 
diffusely spread
 
five different nerve fiber populations
 
Innervated groups
 
intrapulmonary airways
 
lung physiologists
 
mammalian lungs
 
Microscopic data
 
neuroendocrine cells
 
physiological lung receptors
 
present understanding
 
present work
 
proposed functional hypotheses
 
recent reviews
 
selectively contact pulmonary NEBs
 
unique vagal nodose sensory innervation