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Journal of Histochemistry and Cytochemistry
Volume 52 (3): 379-390, 2004
Copyright ©The Histochemical Society, Inc.

Innervation of Pulmonary Neuroendocrine Cells and Neuroepithelial Bodies in Developing Rabbit Lung

Jie Pan, Herman Yeger and Ernest Cutz

Division of Pathology, Department of Pediatric Laboratory Medicine, The Research Institute, The Hospital for Sick Children, and Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada

Correspondence to: Dr. Ernest Cutz, Div. of Pathology, Dept. of Paediatric Laboratory Medicine, The Hospital for Sick Children, 555 University Avenue Toronto, Ontario, Canada, M5G 1X8. E-mail: ernest.cutz{at}sickkids.ca

We investigated the development of innervation of the pulmonary neuroendocrine cell (PNEC) system composed of single cells and organoid cell clusters, neuroepithelial bodies (NEB) in rabbit fetal and neonatal lungs. To visualize the nerve fibers and their contacts with PNECs/NEBs, we used confocal microscopy and multilabel immunohistochemistry (IHC) with pan-neural marker, synaptic vesicle protein 2 (SV2), and serotonin (5-HT) as markers for PNECs/NEBs, and smooth muscle actin or cytokeratin to identify airway landmarks. The numbers and distribution of PNEC/NEB at different stages of lung development (E16, 18, 21, 26, and P2) and the density of innervation were quantified. First PNECs immunoreactive for 5-HT were identified in primitive airway epithelium at E18 as single cells or as small cell clusters with or without early nerve contacts. At E21 a significant increase in the number of PNECs with formation of early innervated NEB corpuscules was observed. The overall numbers of PNECs/NEBs and the density of mucosal, submucosal, and intercorpuscular innervation increased with progressing gestation and peaked postnataly (P2). At term, the majority of NEBs and single PNECs within airway mucosa possessed neural contacts. Such an extensive and complex innervation of the PNEC system indicates a multifunctional role in developing lung and during neonatal adaptation.

(J Histochem Cytochem 52:379–389, 2004)

Key Words: pulmonary neuroendocrine • cells • innervation • development


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[Abstract] [Full Text] [PDF]



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