The Pulmonary Neuroepithelial Body Microenvironment: A Multifunctional Unit in the Airway Epithelium

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This monograph sheds new light on pulmonary sensory receptors. Diving into the pulmonary microenvironment, the book focuses on the role of pulmonary neuroepithelial bodies (NEBs) as potential receptors and effectors, able to store and release neurotransmitters. It explores NEBs as potential stem cell niche and highlights the multidisciplinary approach taken to identify and study NEBs, including functional morphological investigation, live cell imaging, genetic models, and laser microdissection combined with gene expression analysis.

Complexly organized NEBs are an integral part of the intrapulmonary airway epithelium of all air-breathing vertebrates. For decades a quest has been going on to unravel the functional significance of these intriguing structures that appear to be modified in the course of many pulmonary diseases. The NEB microenvironment (ME) is composed of organoid clusters of pulmonary neuroendocrine cells (PNECs) that are able to store and release neurotransmitters and are closely contacted by extensive nerve terminals, emphasizing a potential receptor/effector role and probable signalling to the central nervous system. PNECs are largely shielded from the airway lumen by a special type of Clara cells, the Clara-like cells, with potential stem cell characteristics. So far, functional studies of the pulmonary NEB ME revealed that PNECs can be activated by various mechanical and chemical stimuli, resulting in a calcium-mediated release of neurotransmitters. In the past decades, a number of publications have exposed NEBs as potential hypoxia sensors. Recent experimental evidence unveiled that the NEB ME is a quiescent stem cell niche in healthy postnatal lungs, and silencing may involve bone morphogenetic protein signalling mediated by vagal afferents. Only an integrated approach that takes all current information into account will be able to explain the full role of the pulmonary NEB ME in health and disease.

This highly informative and carefully presented book, provides insights for researchers, PhD students with an interest in (bio)medical and veterinary science, especially in the field of the autonomic innervation of the lung, chemo-and mechanoreceptors

Author(s): Inge Brouns, Line Verckist, Isabel Pintelon, Jean-Pierre Timmermans, Dirk Adriaensen
Series: Advances in Anatomy, Embryology and Cell Biology, 233
Publisher: Springer
Year: 2021

Language: English
Pages: 117
City: Cham

Acknowledgements
Abstract
Contents
About the Authors
List of Abbreviations
Chapter 1: Pulmonary Sensory Receptors
1.1 Sensory Nerves in the Airways
1.2 Intrapulmonary Myelinated Vagal Sensory Airway Receptors
1.3 Why Focussing on the Pulmonary Neuroepithelial Body (NEB) Microenvironment (ME)?
Chapter 2: The Pulmonary NEB ME Is a Complex Intraepithelial Unit
2.1 Components of the NEB ME
2.1.1 Pulmonary Neuroendocrine Cells (PNECs)
2.1.2 Clara-Like Cells (CLCs)
2.1.3 Innervation of the NEB ME
2.2 Receptor-Effector Properties of the Pulmonary NEB ME
Chapter 3: Studying the Pulmonary NEB ME: A Multidisciplinary Approach
3.1 Functional Morphological Characteristics of the NEB ME
3.2 Genetically Engineered Mouse Models to Study the NEB ME
3.3 3D-Imaging and -Analysis of NEBs in Airway Whole Mount and in Cleared Whole Lungs
3.4 Models and Techniques for Functional Live Cell Imaging (LCI) of the NEB ME
3.5 Laser Microdissection and Selective Gene Expression Analysis of the NEB ME
Chapter 4: Functional Exploration of the Pulmonary NEB ME
4.1 Mechanosensing in the NEB ME
4.2 Chemosensing in the NEB ME
4.2.1 Oxygen Sensing in the NEB ME
4.2.2 Activation of the NEB ME by Cigarette Smoke and Nicotine
4.2.3 Sensing Extracellular Ca2+ in the NEB ME
4.2.4 Hypercapnia and H+ Sensing
4.3 The Pulmonary NEB ME: A Unique Stem Cell Niche in the Airway Epithelium?
4.3.1 The NEB ME During Lung Development and After Airway Injury
4.3.1.1 Ontogenetic Development and Importance of the NEB ME
4.3.1.2 Importance of the NEB ME for Epithelial Regeneration After Injury
4.3.2 Modification of the NEB ME Related to Perinatal and Postnatal Disorders
4.3.3 Selective Gene Expression in the Postnatal NEB ME: Special Focus on Stem Cell Characteristics
4.3.4 Selective Activation and Proliferation of a Quiescent Stem Cell Population in the NEB ME by Transient Acute Lung Inflamm...
4.3.5 Silencing Stem Cells in the Healthy Pulmonary NEB ME: Involvement of BMP Signalling
Chapter 5: Concluding Remarks and Future Perspectives
Addendum
References