Innervation of pulmonary neuroendocrine cells and neuroepithelial bodies in developing rabbit lung

Innervation of pulmonary neuroendocrine cells and neuroepithelial bodies in developing rabbit lung
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DOI:
10.1177/002215540405200309
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发表时间:
2004-03-01
影响因子:
3.2
通讯作者:
Cutz, E
Cutz, E
中科院分区:
生物学3区
文献类型:
--
作者:
Pan, J;Yeger, H;Cutz, E

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本实验观察了兔胎肺和新生儿肺神经内分泌细胞(PNEC)系统神经支配的发育。为了可视化神经纤维及其与PNEC/NEB的接触,我们使用共聚焦显微镜和多标记免疫组织化学(IHC),其中泛神经标记物、突触囊泡蛋白2(SV 2)和5-羟色胺(5-HT)作为PNEC/NEB的标记物,平滑肌肌动蛋白或细胞角蛋白用于识别气道标志物。在肺发育的不同阶段(E16,18,21,26和132),PNEC/NEB的数量和分布以及神经支配的密度进行了量化。首先,在E18时在原始气道上皮中鉴定出对5-HT免疫反应的PNEC,其为单个细胞或具有或不具有早期神经接触的小细胞簇。在E21时,观察到PNEC数量显著增加,并形成早期神经支配的NEB小体。PNEC/NEB的总数以及粘膜、粘膜下和细胞间神经支配的密度随着妊娠的进展而增加,并在出生后达到峰值(P2)。足月时,大多数NEB和气道粘膜内的单个PNEC具有神经接触。PNEC系统的这种广泛和复杂的神经支配表明在肺发育和新生儿适应过程中的多功能作用。
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 132) 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.