Pulmonary neuroendocrine cells, airway innervation, and smooth muscle are altered in Cftr null mice
Pulmonary neuroendocrine cells, airway innervation, and smooth muscle are altered in Cftr null mice
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DOI：
10.1165/rcmb.2005-0468oc
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发表时间：
2006-09-01
影响因子：
6.4
通讯作者：
Yeger, Herman
中科院分区：
文献类型：
--
作者：
Pan, Jie;Luk, Catherine;Yeger, Herman
产生胺和肽的肺神经内分泌细胞（PNEC）广泛分布于哺乳动物肺的气道粘膜中，是一种具有呼吸氧传感功能的神经上皮小体（NEB）。这些细胞表达Cftr，因此可能在囊性纤维化（CF）肺病的病理生理学中发挥作用。我们对发育阶段E20、P5、P9和P30的Cftr-/-（无效）、Cftr+/+和Cftr+/-（对照）小鼠的肺切片进行了共聚焦显微镜和形态测定分析，以确定PNEC/NEB的分布、频率和神经支配，气道平滑肌的神经支配和细胞质量，以及使用突触囊泡蛋白2、平滑肌肌动蛋白、和突触素标记物。在E20时，与对照小鼠相比，Cftr-/-小鼠的PNEC/NEB平均数量显著减少，而出生后观察到的数量相当或增加。与对照小鼠相比，CFTR敲除小鼠中的NEB细胞显示出球内神经末梢的显著减少，这与PNEC系统的内在异常一致。与对照小鼠相比，Cftr-/小鼠的气道显示平滑肌神经支配的密度降低（类似于20-30%），平均气道平滑肌质量降低（类似于35%），神经末梢的密度降低（类似于20%）。我们的结论是，CFTR-/-小鼠的气道表现出迄今为止未得到重视的结构变化，影响细胞和神经成分的PNEC系统和气道平滑肌及其神经支配，导致钝化的O-2传感和降低气道紧张。CFTR可能在PNEC系统、肺神经支配和气道平滑肌的发育中发挥作用。
The amine- and peptide-producing pulmonary neuroendocrine cells (PNEC) are widely distributed within the airway mucosa of mammalian lung as solitary cells and innervated clusters, neuroepithelial bodies (NEB), which function as airway O-2 sensors. These cells express Cftr and hence could play a role in the pathophysiology of cystic fibrosis (CF) lung disease. We performed confocal microscopy and morphometric analysis on lung sections from Cftr-/- (null), Cftr+/+, and Cftr+/- (control) mice at developmental stages E20, P5, P9, and P30 to determine the distribution, frequency, and innervation of PNEC/NEB, innervation and cell mass of airway smooth muscle, and neuromuscular junctions using synaptic vesicle protein 2, smooth muscle actin, and synaptophysin markers, respectively. The mean number of PNEC/NEB in Cftr-/- mice was significantly reduced compared with control mice at E20, whereas comparable or increased numbers were observed postnatally. NEB cells in Cftr null mice showed a significant reduction in intracorpuscular nerve endings compared with control mice, which is consistent with an intrinsic abnormality of the PNEC system. The airways of Cftr-/mice showed reduced density (similar to 20-30%) of smooth muscle innervation, decreased mean airway smooth muscle mass (similar to 35%), and reduced density (similar to 20%) of nerve endings compared with control mice. We conclude that the airways of Cftr-/- mice exhibit heretofore unappreciated structural alterations affecting cellular and neural components of the PNEC system and airway smooth muscle and its innervation resulting in blunted O-2 sensing and reduced airway tonus. Cftr could play a role in the development of the PNEC system, lung innervation, and airway smooth muscle.