{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:51:00Z","timestamp":1782237060354,"version":"3.54.5"},"reference-count":108,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>\n                    Although their functions have long been disputed, pulmonary neuroepithelial bodies (NEBs) are now considered complex, multifunctional units implicated in vagal sensory signaling within the brain\u2013lung axis. A widely proposed function of NEBs is that their neuroendocrine cells would be able to sense acute airway hypoxia, triggering Ca\u00b2\u2009\u207a\u2009-dependent transmitter release and the subsequent activation of vagal afferents that transfer the hypoxic information to the central nervous system (CNS). However, physiological evidence for the latter well-documented hypothesis is so far inconclusive. Using a confocal live-cell imaging model, based on murine precision-cut lung slices (PCLSs), this study was designed to directly visualize hypoxia-induced activation of NEB cells, including associated Ca\u00b2\u2009\u207a\u2009-mediated exocytotic events that would support CNS-directed signaling. In PCLSs from prenatal and postnatal C57BL\/6 mice, including GAD67-GFP mice, we monitored changes in intracellular Ca\u00b2\u207a ([Ca\u00b2\u207a]\n                    <jats:sub>i<\/jats:sub>\n                    ), mitochondrial membrane potential, and reactive oxygen species (ROS) during acute and intermittent hypoxia, as well as after ROS scavenging. Whole-mount mouse carotid bodies served as positive controls. Carotid body glomus cells showed robust hypoxia-induced [Ca\u00b2\u207a]\n                    <jats:sub>i<\/jats:sub>\n                    rises, confirming assay sensitivity. In contrast, neither acute (2 or 12% O\u2082) nor intermittent hypoxia elicited [Ca\u00b2\u207a]\n                    <jats:sub>i<\/jats:sub>\n                    increases in NEBs or delayed activation of adjacent Clara-like cells at any developmental stage. NEBs remained responsive to K\n                    <jats:sup>+<\/jats:sup>\n                    -induced depolarization, though excitability appeared to decrease during hypoxia. Hypoxia caused rapid, reversible mitochondrial depolarization in NEBs and ciliated epithelial cells, accompanied by a modest ROS increase in all airway epithelial cells. Tempol did not uncover any [Ca\u00b2\u207a]\n                    <jats:sub>i<\/jats:sub>\n                    responses. Whereas control airway epithelium and carotid body expressed all NADPH oxidase subunits, the NEB microenvironment appeared to lack clear expression of several components. We conclude that mouse NEBs do not exhibit Ca\u00b2\u2009\u207a\u2009-mediated exocytotic responses to hypoxia and that NADPH oxidase is unlikely to function as their O\u2082 sensor. These findings challenge a direct NEB-to-brain signaling pathway for acute hypoxia, but support local, paracrine functions related to airway oxygenation.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0351688","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T17:28:37Z","timestamp":1782235717000},"page":"e0351688","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Are pulmonary neuroepithelial bodies sensors for acute airway hypoxia implicated in the central regulation of breathing?"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9916-0762","authenticated-orcid":true,"given":"Inge","family":"Brouns","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Schnorbusch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2901-4679","authenticated-orcid":true,"given":"Isabel","family":"Pintelon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robrecht","family":"Lembrechts","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian","family":"De Proost","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul J.","family":"Kemp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2506-6252","authenticated-orcid":true,"given":"Jean-Pierre","family":"Timmermans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Adriaensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"issue":"2","key":"pone.0351688.ref001","article-title":"Mapping of the sensory innervation of the mouse lung by specific vagal and dorsal root ganglion neuronal subsets","volume":"9","author":"S-H Kim","year":"2022","journal-title":"eNeuro"},{"issue":"1","key":"pone.0351688.ref002","article-title":"Identification of lung innervating sensory neurons and their target specificity","volume":"322","author":"Y Su","year":"2022","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"2","key":"pone.0351688.ref003","article-title":"Mapping of sensory nerve subsets within the vagal ganglia and the brainstem using reporter mice for Pirt, TRPV1, 5-HT3, and Tac1 expression","volume":"7","author":"SH Kim","year":"2020","journal-title":"eNeuro"},{"key":"pone.0351688.ref004","article-title":"Molecular, anatomical, and functional organization of lung interoceptors","author":"Y Liu","year":"2021","journal-title":"BioRivix"},{"issue":"7903","key":"pone.0351688.ref005","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1038\/s41586-022-04515-5","article-title":"A multidimensional coding architecture of the vagal interoceptive system","volume":"603","author":"Q Zhao","year":"2022","journal-title":"Nature"},{"key":"pone.0351688.ref006","doi-asserted-by":"crossref","first-page":"135505","DOI":"10.1016\/j.neulet.2020.135505","article-title":"Molecular identity, anatomy, gene expression and function of neural crest vs. placode-derived nociceptors in the lower airways","volume":"742","author":"TE Taylor-Clark","year":"2021","journal-title":"Neurosci Lett"},{"key":"pone.0351688.ref007","doi-asserted-by":"crossref","first-page":"103000","DOI":"10.1016\/j.conb.2025.103000","article-title":"Vagal sensory circuits of the lower airway in respiratory physiology: Insights from neuronal diversity","volume":"92","author":"J Li","year":"2025","journal-title":"Curr Opin Neurobiol"},{"issue":"3","key":"pone.0351688.ref008","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1002\/ar.1091720301","article-title":"Neuro-epithelial bodies (neuroreceptor or secretory organs?) in human infant bronchial and bronchiolar epithelium","volume":"172","author":"JM Lauweryns","year":"1972","journal-title":"Anat Rec"},{"issue":"8005","key":"pone.0351688.ref009","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1038\/s41586-024-07144-2","article-title":"A vagal reflex evoked by airway closure","volume":"627","author":"MS Schappe","year":"2024","journal-title":"Nature"},{"issue":"3","key":"pone.0351688.ref010","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1136\/thx.42.3.183","article-title":"Calcitonin gene related peptide immunoreactivity in rat lung: light and electron microscopic study","volume":"42","author":"JM Lauweryns","year":"1987","journal-title":"Thorax"},{"issue":"1","key":"pone.0351688.ref011","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1007\/BF00167597","article-title":"Pulmonary neuroepithelial bodies in neonatal and adult dogs: histochemistry, ultrastructure, and effects of unilateral hilar lung denervation","volume":"173","author":"A Van Lommel","year":"1995","journal-title":"Lung"},{"issue":"3","key":"pone.0351688.ref012","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1159\/000147734","article-title":"Neuroepithelial bodies in relatively mature lungs: an investigation in prenatal and newborn lambs","volume":"153","author":"A van Lommel","year":"1995","journal-title":"Acta Anat (Basel)"},{"issue":"2","key":"pone.0351688.ref013","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0034-5687(99)00018-3","article-title":"Neuroepithelial bodies as airway oxygen sensors","volume":"115","author":"E Cutz","year":"1999","journal-title":"Respir Physiol"},{"issue":"1","key":"pone.0351688.ref014","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1679\/aohc.62.1","article-title":"The pulmonary neuroendocrine system: the past decade","volume":"62","author":"A Van Lommel","year":"1999","journal-title":"Arch Histol Cytol"},{"issue":"4","key":"pone.0351688.ref015","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1023\/A:1026567603514","article-title":"Postnatal maturation of neuroepithelial bodies and carotid body innervation: a quantitative investigation in the rabbit","volume":"29","author":"T Boll\u00e9","year":"2000","journal-title":"J Neurocytol"},{"issue":"3","key":"pone.0351688.ref016","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1152\/japplphysiol.00267.2006","article-title":"Evidence for a role of neuroepithelial bodies as complex airway sensors: comparison with smooth muscle-associated airway receptors","volume":"101","author":"D Adriaensen","year":"2006","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0351688.ref017","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/ar.a.10007","article-title":"Functional morphology of pulmonary neuroepithelial bodies: extremely complex airway receptors","author":"D Adriaensen","year":"2003","journal-title":"Anat Rec"},{"issue":"1","key":"pone.0351688.ref018","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.resp.2008.09.012","article-title":"Lung afferent activity: implications for respiratory sensation","volume":"167","author":"J Widdicombe","year":"2009","journal-title":"Respir Physiol Neurobiol"},{"issue":"1","key":"pone.0351688.ref019","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s00418-008-0495-7","article-title":"Neurochemical pattern of the complex innervation of neuroepithelial bodies in mouse lungs","volume":"131","author":"I Brouns","year":"2009","journal-title":"Histochem Cell Biol"},{"issue":"1","key":"pone.0351688.ref020","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1164\/rccm.201412-2293OC","article-title":"Morphologic characterization of nerves in whole-mount airway biopsies","volume":"192","author":"PW West","year":"2015","journal-title":"Am J Respir Crit Care Med"},{"issue":"7636","key":"pone.0351688.ref021","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1038\/nature20793","article-title":"Piezo2 senses airway stretch and mediates lung inflation-induced apnoea","volume":"541","author":"K Nonomura","year":"2017","journal-title":"Nature"},{"issue":"5","key":"pone.0351688.ref022","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/labinvest.3700412","article-title":"Functional facets of the pulmonary neuroendocrine system","volume":"86","author":"RI Linnoila","year":"2006","journal-title":"Lab Invest"},{"key":"pone.0351688.ref023","first-page":"191","article-title":"Neuroepithelial bodies and solitary small-granule cells.","volume-title":"Lung Cell Biology","author":"SP Sorokin","year":"1989"},{"issue":"3","key":"pone.0351688.ref024","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1007\/s10571-022-01238-z","article-title":"Functional two-way crosstalk between brain and lung: the brain-lung axis","volume":"43","author":"C Li","year":"2023","journal-title":"Cell Mol Neurobiol"},{"key":"pone.0351688.ref025","doi-asserted-by":"crossref","first-page":"1438188","DOI":"10.3389\/fnins.2024.1438188","article-title":"Pulmonary neuroendocrine cells: crucial players in respiratory function and airway-nerve communication","volume":"18","author":"A Thakur","year":"2024","journal-title":"Front Neurosci"},{"issue":"4","key":"pone.0351688.ref026","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1002\/ar.25171","article-title":"The pulmonary neuroepithelial body microenvironment represents an underestimated multimodal component in airway sensory pathways","volume":"308","author":"I Brouns","year":"2025","journal-title":"Anat Rec (Hoboken)"},{"key":"pone.0351688.ref027","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-3-030-65817-5_1","article-title":"The pulmonary neuroepithelial body microenvironment. A multifunctional unit in the airway epithelium","volume":"233","author":"I Brouns","year":"2021","journal-title":"Adv Anat Embryol Cell Biol"},{"issue":"4","key":"pone.0351688.ref028","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1007\/BF00583438","article-title":"Neuro-epithelial bodies in the respiratory mucosa of various mammals. A light optical, histochemical and ultrastructural investigation","volume":"135","author":"JM Lauweryns","year":"1972","journal-title":"Z Zellforsch Mikrosk Anat"},{"key":"pone.0351688.ref029","first-page":"517","article-title":"Die \u201cHelle Zelle\u201d der Bronchialschleimhaut und ihre Beziehungen zum Problem der Chemoreceptoren","volume":"60","author":"F Fr\u00f6hlich","year":"1949","journal-title":"Frankf Z Pathol"},{"key":"pone.0351688.ref030","first-page":"73","article-title":"\u00dcber die Argyrophilie des Helle-Zellen-Systems im Bronchialbaum des Menschen","volume":"61","author":"F Feyrter","year":"1954","journal-title":"Zeitschrift f\u00fcr Mikroskopie und Anatomische Forschung"},{"key":"pone.0351688.ref031","first-page":"395","article-title":"Functional implications of extensive new data on the innervation of pulmonary neuroepithelial bodies","volume":"106","author":"D Adriaensen","year":"2001","journal-title":"Ital J Anat Embryol"},{"issue":"3","key":"pone.0351688.ref032","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1007\/BF00214575","article-title":"Occurrence and distribution of calcitonin gene-related peptide in the mammalian respiratory tract and middle ear","volume":"241","author":"R Uddman","year":"1985","journal-title":"Cell Tissue Res"},{"key":"pone.0351688.ref033","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1113\/jphysiol.2001.013071","article-title":"Hypoxia-induced secretion of serotonin from intact pulmonary neuroepithelial bodies in neonatal rabbit","volume":"539","author":"XW Fu","year":"2002","journal-title":"J Physiol"},{"issue":"1","key":"pone.0351688.ref034","first-page":"119","article-title":"Ultrastructural colocalization of the bioactive mediators 5-hydroxytryptamine and bombesin in endocrine cells of human fetal airways","volume":"246","author":"RD Dey","year":"1986","journal-title":"Cell Tissue Res"},{"issue":"1","key":"pone.0351688.ref035","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/ar.1092360111","article-title":"Neuroendocrine cells and nerves of the lung","volume":"236","author":"D Adriaensen","year":"1993","journal-title":"Anat Rec"},{"issue":"6","key":"pone.0351688.ref036","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1053\/j.semdp.2015.08.001","article-title":"Hyperplasia of pulmonary neuroendocrine cells in infancy and childhood","volume":"32","author":"E Cutz","year":"2015","journal-title":"Semin Diagn Pathol"},{"issue":"1","key":"pone.0351688.ref037","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.semcdb.2012.09.003","article-title":"Recent advances and contraversies on the role of pulmonary neuroepithelial bodies as airway sensors","volume":"24","author":"E Cutz","year":"2013","journal-title":"Semin Cell Dev Biol"},{"key":"pone.0351688.ref038","first-page":"1","article-title":"Novel insights in the neurochemistry and function of pulmonary sensory receptors","volume":"211","author":"I Brouns","year":"2012","journal-title":"Adv Anat Embryol Cell Biol"},{"key":"pone.0351688.ref039","article-title":"Neuroendocrinology of the lung revealed by single-cell RNA sequencing","volume":"11","author":"CS Kuo","year":"2022","journal-title":"Elife"},{"issue":"4","key":"pone.0351688.ref040","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1096\/fj.08-109579","article-title":"Purinergic signaling in the pulmonary neuroepithelial body microenvironment unraveled by live cell imaging","volume":"23","author":"I De Proost","year":"2009","journal-title":"FASEB J"},{"issue":"4","key":"pone.0351688.ref041","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1124\/pr.111.005389","article-title":"Purinergic signaling in the airways","volume":"64","author":"G Burnstock","year":"2012","journal-title":"Pharmacol Rev"},{"key":"pone.0351688.ref042","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/j.coph.2004.01.010","article-title":"Purinergic signalling in the lung: important in asthma and COPD?","volume":"4","author":"D Adriaensen","year":"2004","journal-title":"Curr Opin Pharmacol"},{"issue":"5","key":"pone.0351688.ref043","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s00418-013-1093-x","article-title":"GABAergic signaling in the pulmonary neuroepithelial body microenvironment: functional imaging in GAD67-GFP mice","volume":"140","author":"K Schnorbusch","year":"2013","journal-title":"Histochem Cell Biol"},{"issue":"1","key":"pone.0351688.ref044","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12931-018-0915-8","article-title":"Selective activation and proliferation of a quiescent stem cell population in the neuroepithelial body microenvironment","volume":"19","author":"L Verckist","year":"2018","journal-title":"Respir Res"},{"key":"pone.0351688.ref045","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1007\/978-94-007-4584-1_22","article-title":"Precision-cut vibratome slices allow functional live cell imaging of the pulmonary neuroepithelial body microenvironment in fetal mice","volume":"758","author":"K Schnorbusch","year":"2012","journal-title":"Adv Exp Med Biol"},{"issue":"3","key":"pone.0351688.ref046","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/j.cell.2015.03.022","article-title":"Vagal sensory neuron subtypes that differentially control breathing","volume":"161","author":"RB Chang","year":"2015","journal-title":"Cell"},{"issue":"5","key":"pone.0351688.ref047","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.050620","article-title":"Investigating pulmonary neuroendocrine cells in human respiratory diseases with airway models","volume":"17","author":"N Candeli","year":"2024","journal-title":"Dis Model Mech"},{"issue":"3","key":"pone.0351688.ref048","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1165\/rcmb.2012-0068OC","article-title":"Neuroepithelial bodies as mechanotransducers in the intrapulmonary airway epithelium: involvement of TRPC5","volume":"47","author":"R Lembrechts","year":"2012","journal-title":"Am J Respir Cell Mol Biol"},{"key":"pone.0351688.ref049","doi-asserted-by":"crossref","first-page":"4490","DOI":"10.1242\/jcs.131656","article-title":"Functional expression of the multimodal extracellular calcium-sensing receptor in pulmonary neuroendocrine cells","volume":"126","author":"R Lembrechts","year":"2013","journal-title":"J Cell Sci"},{"issue":"6442","key":"pone.0351688.ref050","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/365153a0","article-title":"Oxygen sensing in airway chemoreceptors","volume":"365","author":"C Youngson","year":"1993","journal-title":"Nature"},{"key":"pone.0351688.ref051","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1201\/b10181-17","article-title":"Oxygen sensing in mammalian pulmonary neuroepithelial bodies.","volume-title":"Airway chemoreceptors in the vertebrates Structure, evolution and function","author":"E Cutz","year":"2009"},{"issue":"3","key":"pone.0351688.ref052","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/j.coph.2011.04.003","article-title":"Pulmonary neuroepithelial bodies as airway sensors: putative role in the generation of dyspnea","volume":"11","author":"NJ Domnik","year":"2011","journal-title":"Curr Opin Pharmacol"},{"issue":"12","key":"pone.0351688.ref053","doi-asserted-by":"crossref","DOI":"10.1242\/dmm.046920","article-title":"Pulmonary neuroendocrine cells: physiology, tissue homeostasis and disease","volume":"13","author":"M Noguchi","year":"2020","journal-title":"Dis Model Mech"},{"key":"pone.0351688.ref054","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/bs.ctdb.2018.12.002","article-title":"Consider the lung as a sensory organ: a tip from pulmonary neuroendocrine cells","volume":"132","author":"A Garg","year":"2019","journal-title":"Curr Top Dev Biol"},{"key":"pone.0351688.ref055","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1469-7793.1999.139af.x","article-title":"Selective modulation of membrane currents by hypoxia in intact airway chemoreceptors from neonatal rabbit","volume":"514","author":"XW Fu","year":"1999","journal-title":"J Physiol"},{"issue":"4","key":"pone.0351688.ref056","article-title":"O2-sensitive K+ channels in neuroepithelial body-derived small cell carcinoma cells of the human lung","volume":"275","author":"I O\u2019Kelly","year":"1998","journal-title":"Am J Physiol"},{"issue":"1","key":"pone.0351688.ref057","article-title":"Potential identification of the O2-sensitive K+ current in a human neuroepithelial body-derived cell line","volume":"276","author":"I O\u2019Kelly","year":"1999","journal-title":"Am J Physiol"},{"issue":"11","key":"pone.0351688.ref058","first-page":"7684","article-title":"O(2) sensing by airway chemoreceptor-derived cells. Protein kinase c activation reveals functional evidence for involvement of NADPH oxidase","volume":"275","author":"I O\u2019Kelly","year":"2000","journal-title":"J Biol Chem"},{"issue":"28","key":"pone.0351688.ref059","doi-asserted-by":"crossref","first-page":"26499","DOI":"10.1074\/jbc.M010357200","article-title":"Combined antisense and pharmacological approaches implicate hTASK as an airway O(2) sensing K(+) channel","volume":"276","author":"ME Hartness","year":"2001","journal-title":"J Biol Chem"},{"issue":"4","key":"pone.0351688.ref060","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0166-2236(94)90084-1","article-title":"Oxygen-sensitive ion channels: how ubiquitous are they?","volume":"17","author":"J L\u00f3pez-Barneo","year":"1994","journal-title":"Trends Neurosci"},{"issue":"23","key":"pone.0351688.ref061","doi-asserted-by":"crossref","first-page":"13182","DOI":"10.1073\/pnas.93.23.13182","article-title":"NADPH-oxidase and a hydrogen peroxide-sensitive K+ channel may function as an oxygen sensor complex in airway chemoreceptors and small cell lung carcinoma cell lines","volume":"93","author":"D Wang","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"8","key":"pone.0351688.ref062","doi-asserted-by":"crossref","first-page":"4374","DOI":"10.1073\/pnas.97.8.4374","article-title":"NADPH oxidase is an O2 sensor in airway chemoreceptors: evidence from K+ current modulation in wild-type and oxidase-deficient mice","volume":"97","author":"XW Fu","year":"2000","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"pone.0351688.ref063","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1002\/(SICI)1097-0029(19970401)37:1<101::AID-JEMT10>3.0.CO;2-V","article-title":"Immunocytochemical localization on O2-sensing protein (NADPH oxidase) in chemoreceptor cells","volume":"37","author":"C Youngson","year":"1997","journal-title":"Microsc Res Tech"},{"issue":"3","key":"pone.0351688.ref064","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1186\/rr51","article-title":"Acute oxygen sensing: diverse but convergent mechanisms in airway and arterial chemoreceptors","volume":"2","author":"C Peers","year":"2001","journal-title":"Respir Res"},{"key":"pone.0351688.ref065","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/j.1749-6632.2009.05025.x","article-title":"Enzyme-linked oxygen sensing by potassium channels","volume":"1177","author":"PJ Kemp","year":"2009","journal-title":"Ann N Y Acad Sci"},{"key":"pone.0351688.ref066","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1007\/978-90-481-2259-2_4","article-title":"Enzyme-linked acute oxygen sensing in airway and arterial chemoreceptors--invited article","volume":"648","author":"JP Kemp","year":"2009","journal-title":"Adv Exp Med Biol"},{"issue":"4","key":"pone.0351688.ref067","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1007\/s00418-007-0318-2","article-title":"Pulmonary expression of voltage-gated calcium channels: special reference to sensory airway receptors","volume":"128","author":"I De Proost","year":"2007","journal-title":"Histochem Cell Biol"},{"issue":"1","key":"pone.0351688.ref068","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/ar.a.10008","article-title":"Acute oxygen sensing in cellular models: relevance to the physiology of pulmonary neuroepithelial and carotid bodies","volume":"270","author":"PJ Kemp","year":"2003","journal-title":"Anat Rec A Discov Mol Cell Evol Biol"},{"issue":"1","key":"pone.0351688.ref069","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/aja.1001730102","article-title":"Development of neuroepithelial bodies in intact and cultured lungs of fetal rats","volume":"173","author":"VH Carabba","year":"1985","journal-title":"Am J Anat"},{"issue":"6","key":"pone.0351688.ref070","first-page":"672","article-title":"In vitro characteristics of pulmonary neuroendocrine cells isolated from rabbit fetal lung. I. Effects of culture media and nerve growth factor","volume":"53","author":"E Cutz","year":"1985","journal-title":"Lab Invest"},{"issue":"1","key":"pone.0351688.ref071","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1165\/ajrcmb\/6.1.63","article-title":"Isolation and culture of neuroendocrine cells from fetal rabbit lung using immunomagnetic techniques","volume":"6","author":"V Speirs","year":"1992","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"pone.0351688.ref072","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ar.1092360108","article-title":"An overview of culture and isolation methods suitable for in vitro studies on pulmonary neuroendocrine cells","volume":"236","author":"V Speirs","year":"1993","journal-title":"Anat Rec"},{"issue":"4","key":"pone.0351688.ref073","article-title":"Characterization of slowly inactivating KV{alpha} current in rabbit pulmonary neuroepithelial bodies: effects of hypoxia and nicotine","volume":"293","author":"XW Fu","year":"2007","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"3","key":"pone.0351688.ref074","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1177\/002215540405200309","article-title":"Innervation of pulmonary neuroendocrine cells and neuroepithelial bodies in developing rabbit lung","volume":"52","author":"J Pan","year":"2004","journal-title":"J Histochem Cytochem"},{"issue":"5","key":"pone.0351688.ref075","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1007\/s00408-016-9908-x","article-title":"Oxygen sensing in early life","volume":"194","author":"C Caravagna","year":"2016","journal-title":"Lung"},{"issue":"2","key":"pone.0351688.ref076","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1002\/j.2040-4603.2021.tb00155.x","article-title":"Perinatal hypoxemia and oxygen sensing","volume":"11","author":"GC Mouradian","year":"2021","journal-title":"Compr Physiol"},{"issue":"2","key":"pone.0351688.ref077","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1165\/rcmb.2008-0011OC","article-title":"Functional live cell imaging of the pulmonary neuroepithelial body microenvironment","volume":"39","author":"I De Proost","year":"2008","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"pone.0351688.ref078","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/s00441-005-1111-y","article-title":"Selective visualisation of neuroepithelial bodies in vibratome slices of living lung by 4-Di-2-ASP in various animal species","volume":"321","author":"I Pintelon","year":"2005","journal-title":"Cell Tissue Res"},{"issue":"1","key":"pone.0351688.ref079","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1186\/s12931-017-0571-4","article-title":"Selective gene expression analysis of the neuroepithelial body microenvironment in postnatal lungs with special interest for potential stem cell characteristics","volume":"18","author":"L Verckist","year":"2017","journal-title":"Respir Res"},{"issue":"1","key":"pone.0351688.ref080","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12931-019-1131-x","article-title":"Use of precision cut lung slices as a translational model for the study of lung biology","volume":"20","author":"G Liu","year":"2019","journal-title":"Respir Res"},{"issue":"12","key":"pone.0351688.ref081","doi-asserted-by":"crossref","first-page":"767","DOI":"10.3390\/bioengineering9120767","article-title":"Application of precision-cut lung slices as an in vitro model for research of inflammatory respiratory diseases","volume":"9","author":"Y Liu","year":"2022","journal-title":"Bioengineering (Basel)"},{"issue":"22","key":"pone.0351688.ref082","doi-asserted-by":"crossref","DOI":"10.14814\/phy2.15873","article-title":"Neuropeptide stimulation of physiological and immunological responses in precision-cut lung slices","volume":"11","author":"B Patlin","year":"2023","journal-title":"Physiol Rep"},{"key":"pone.0351688.ref083","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1146\/annurev-physiol-020518-114427","article-title":"Physiology of the carotid body: from molecules to disease","volume":"82","author":"P Ortega-S\u00e1enz","year":"2020","journal-title":"Annu Rev Physiol"},{"issue":"6","key":"pone.0351688.ref084","doi-asserted-by":"crossref","first-page":"2287","DOI":"10.1152\/jappl.2000.88.6.2287","article-title":"Oxygen sensing by the carotid body chemoreceptors","volume":"88","author":"NR Prabhakar","year":"2000","journal-title":"J Appl Physiol (1985)"},{"issue":"3","key":"pone.0351688.ref085","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.pbiomolbio.2005.07.001","article-title":"Oxygen sensing in the body","volume":"91","author":"S Lahiri","year":"2006","journal-title":"Prog Biophys Mol Biol"},{"issue":"5","key":"pone.0351688.ref086","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1183\/09031936.00056408","article-title":"Carotid body oxygen sensing","volume":"32","author":"J L\u00f3pez-Barneo","year":"2008","journal-title":"Eur Respir J"},{"key":"pone.0351688.ref087","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1749-6632.2009.05033.x","article-title":"Oxygen sensing in the carotid body","volume":"1177","author":"J L\u00f3pez-Barneo","year":"2009","journal-title":"Ann N Y Acad Sci"},{"issue":"3","key":"pone.0351688.ref088","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.resp.2010.08.010","article-title":"Mechanisms for acute oxygen sensing in the carotid body","volume":"174","author":"C Peers","year":"2010","journal-title":"Respir Physiol Neurobiol"},{"issue":"8","key":"pone.0351688.ref089","doi-asserted-by":"crossref","DOI":"10.1152\/ajplung.00208.2014","article-title":"Pulmonary neuroepithelial bodies are polymodal airway sensors: evidence for CO2\/H+ sensing","volume":"308","author":"S Livermore","year":"2015","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"1","key":"pone.0351688.ref090","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1152\/japplphysiol.00809.2003","article-title":"Peripheral chemoreceptors in health and disease","volume":"96","author":"NR Prabhakar","year":"2004","journal-title":"J Appl Physiol (1985)"},{"key":"pone.0351688.ref091","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1113\/jphysiol.2006.114033","article-title":"Heterozygous HIF-1alpha deficiency impairs carotid body-mediated systemic responses and reactive oxygen species generation in mice exposed to intermittent hypoxia","volume":"577","author":"Y-J Peng","year":"2006","journal-title":"J Physiol"},{"key":"pone.0351688.ref092","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/978-90-481-2259-2_49","article-title":"The role of NOX2 and \u201cnovel oxidases\u201d in airway chemoreceptor O(2) sensing","volume":"648","author":"E Cutz","year":"2009","journal-title":"Adv Exp Med Biol"},{"issue":"6","key":"pone.0351688.ref093","doi-asserted-by":"crossref","first-page":"890","DOI":"10.3390\/antiox10060890","article-title":"NADPH Oxidases (NOX): an overview from discovery, molecular mechanisms to physiology and pathology","volume":"10","author":"A Vermot","year":"2021","journal-title":"Antioxidants (Basel)"},{"issue":"4","key":"pone.0351688.ref094","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1007\/BF00306722","article-title":"Hypoxia-sensitive neuro-epithelial bodies. Intrapulmonary secretory neuroreceptors, modulated by the CNS","volume":"145","author":"JM Lauweryns","year":"1973","journal-title":"Z Zellforsch Mikrosk Anat"},{"issue":"1","key":"pone.0351688.ref095","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1002\/ar.1092360109","article-title":"Cell biology of pulmonary neuroepithelial bodies--validation of an in vitro model. I. Effects of hypoxia and Ca2+ ionophore on serotonin content and exocytosis of dense core vesicles","volume":"236","author":"E Cutz","year":"1993","journal-title":"Anat Rec"},{"issue":"5","key":"pone.0351688.ref096","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1165\/rcmb.4843","article-title":"Cystic fibrosis transmembrane conductance regulator modulates neurosecretory function in pulmonary neuroendocrine cell-related tumor cell line models","volume":"27","author":"J Pan","year":"2002","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"1","key":"pone.0351688.ref097","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/ar.1092360113","article-title":"Calcitonin gene-related peptide and pulmonary hypertension in experimental hypoxia","volume":"236","author":"DR Springall","year":"1993","journal-title":"Anat Rec"},{"issue":"5","key":"pone.0351688.ref098","doi-asserted-by":"crossref","first-page":"369","DOI":"10.3109\/00365519509104975","article-title":"Acute alveolar hypoxia increases endothelin-1 release but decreases release of calcitonin gene-related peptide in isolated perfused rat lungs","volume":"55","author":"E Helset","year":"1995","journal-title":"Scand J Clin Lab Invest"},{"issue":"1","key":"pone.0351688.ref099","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0167-0115(98)00007-X","article-title":"Sensory CGRP depletion by capsaicin exacerbates hypoxia-induced pulmonary hypertension in rats","volume":"74","author":"S Tjen-A-Looi","year":"1998","journal-title":"Regul Pept"},{"issue":"1","key":"pone.0351688.ref100","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.resp.2008.02.014","article-title":"Release of neuroendocrine products in the pulmonary circulation during intermittent hypoxia in isolated rat lung","volume":"162","author":"S S\u00f8rhaug","year":"2008","journal-title":"Respir Physiol Neurobiol"},{"issue":"3","key":"pone.0351688.ref101","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/path.1711550312","article-title":"Increased intracellular levels of calcitonin gene-related peptide-like immunoreactivity in pulmonary endocrine cells of hypoxic rats","volume":"155","author":"DR Springall","year":"1988","journal-title":"J Pathol"},{"issue":"6","key":"pone.0351688.ref102","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1165\/ajrcmb\/3.6.587","article-title":"Quantitative immunocytochemistry shows calcitonin gene-related peptide-like immunoreactivity in lung neuroendocrine cells is increased by chronic hypoxia in the rat","volume":"3","author":"JT McBride","year":"1990","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"5","key":"pone.0351688.ref103","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1165\/ajrcmb\/9.5.467","article-title":"Early changes in the calcitonin gene-related peptide (CGRP) content of pulmonary endocrine cells concomitant with vascular remodeling in the hypoxic rat","volume":"9","author":"M Roncalli","year":"1993","journal-title":"Am J Respir Cell Mol Biol"},{"issue":"3","key":"pone.0351688.ref104","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1152\/physrev.00039.2015","article-title":"Vagal afferent innervation of the airways in health and disease","volume":"96","author":"SB Mazzone","year":"2016","journal-title":"Physiol Rev"},{"issue":"6274","key":"pone.0351688.ref105","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1126\/science.aad7969","article-title":"Pulmonary neuroendocrine cells function as airway sensors to control lung immune response","volume":"351","author":"K Branchfield","year":"2016","journal-title":"Science"},{"issue":"6393","key":"pone.0351688.ref106","article-title":"Pulmonary neuroendocrine cells amplify allergic asthma responses","volume":"360","author":"P Sui","year":"2018","journal-title":"Science"},{"issue":"6","key":"pone.0351688.ref107","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1165\/rcmb.2018-0179OC","article-title":"Pulmonary neuroendocrine cells secrete \u03b3-aminobutyric acid to induce goblet cell hyperplasia in primate models","volume":"60","author":"J Barrios","year":"2019","journal-title":"Am J Respir Cell Mol Biol"},{"key":"pone.0351688.ref108","first-page":"69","article-title":"Hyperplasia and hypertrophy of pulmonary neuroepithelial bodies, presumed airway hypoxia sensors, in hypoxia-inducible factor prolyl hydroxylase-deficient mice","volume":"4","author":"J Pan","year":"2016","journal-title":"Hypoxia (Auckl)"}],"container-title":["PLOS 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