Laboratory of Cell Biology and Histology, Department of Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610, Wilrijk, Antwerpen, Belgium.
Respir Res. 2018 Oct 26;19(1):207. doi: 10.1186/s12931-018-0915-8.
The microenvironment (ME) of neuroepithelial bodies (NEBs) harbors densely innervated groups of pulmonary neuroendocrine cells that are covered by Clara-like cells (CLCs) and is believed to be important during development and for adult airway epithelial repair after severe injury. Yet, little is known about its potential stem cell characteristics in healthy postnatal lungs.
Transient mild lung inflammation was induced in mice via a single low-dose intratracheal instillation of lipopolysaccharide (LPS). Bronchoalveolar lavage fluid (BALF), collected 16 h after LPS instillation, was used to challenge the NEB ME in ex vivo lung slices of control mice. Proliferating cells in the NEB ME were identified and quantified following simultaneous LPS instillation and BrdU injection.
The applied LPS protocol induced very mild and transient lung injury. Challenge of lung slices with BALF of LPS-treated mice resulted in selective Ca-mediated activation of CLCs in the NEB ME of control mice. Forty-eight hours after LPS challenge, a remarkably selective and significant increase in the number of divided (BrdU-labeled) cells surrounding NEBs was observed in lung sections of LPS-challenged mice. Proliferating cells were identified as CLCs.
A highly reproducible and minimally invasive lung inflammation model was validated for inducing selective activation of a quiescent stem cell population in the NEB ME. The model creates new opportunities for unraveling the cellular mechanisms/pathways regulating silencing, activation, proliferation and differentiation of this unique postnatal airway epithelial stem cell population.
神经上皮体（NEB）的微环境（ME）中存在着密集的神经内分泌细胞群，这些细胞被克拉拉样细胞（CLC）所覆盖，被认为在发育过程中以及在严重损伤后成人气道上皮修复中具有重要作用。然而，对于健康出生后肺中的潜在干细胞特征，我们知之甚少。
通过单次低剂量气管内滴注脂多糖（LPS）诱导小鼠短暂轻度肺炎症。在 LPS 滴注后 16 小时收集支气管肺泡灌洗液（BALF），用于挑战对照小鼠的离体肺切片中的 NEB ME。在 LPS 注射和 BrdU 注射的同时，鉴定和定量 NEB ME 中的增殖细胞。
应用的 LPS 方案引起了非常轻微和短暂的肺损伤。用 LPS 处理小鼠的 BALF 挑战肺切片，导致对照小鼠的 NEB ME 中 CLC 选择性地钙介导激活。在 LPS 挑战后 48 小时，在 LPS 挑战小鼠的肺切片中观察到围绕 NEB 的分裂（BrdU 标记）细胞数量显著且选择性增加。增殖细胞被鉴定为 CLCs。
验证了一种高度可重复且微创的肺炎症模型，用于诱导 NEB ME 中静止干细胞群的选择性激活。该模型为揭示调节这种独特的出生后气道上皮干细胞群沉默、激活、增殖和分化的细胞机制/途径提供了新的机会。
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