Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance.

Airway Epithelial Nucleotide Release Contributes to Mucociliary Clearance.
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DOI:
10.3390/life11050430
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发表时间:
2021-05-11
期刊:
Life (Basel, Switzerland)
影响因子:
--
通讯作者:
Lazarowski ER
Lazarowski ER
中科院分区:
其他
文献类型:
--
作者:
van Heusden C;Grubb BR;Button B;Lazarowski ER

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粘膜钙清除率(MCC)是肺部防御的主要组成部分。在健康中,周围层(PCL)是最佳水合的,因此充当有效的润滑层,粘液层通过纤毛力移动。气道表面脱水和过度浓缩的粘液的产生是慢性阻塞性肺部疾病(例如囊性纤维化(CF)和慢性支气管炎(CB))的共同特征。粘液水合是由电解质转运活性驱动的,而电解质转运活性又受气道上皮嘌呤能受体的调节。这些受体的活性由ATP的细胞外浓度及其代谢产物腺苷控制。囊泡和进行的途径有助于从气道上皮细胞中释放ATP。在这项研究中,我们回顾了导致这些途径主要组成部分的证据:(a)囊泡核苷酸转运蛋白转运蛋白Vnut(SLC17A9基因的乘积),ATP转运蛋白介导ATP存储在(并释放出来)粘蛋白营养剂和分泌囊泡; (b)在非监动气道上皮细胞中表达的ATP导管泛素1。我们进一步说明,泛毒素1的消融至少部分降低了气道表面液体(ASL)体积产生,纤毛打击和MCC速率。
Mucociliary clearance (MCC) is a dominant component of pulmonary host defense. In health, the periciliary layer (PCL) is optimally hydrated, thus acting as an efficient lubricant layer over which the mucus layer moves by ciliary force. Airway surface dehydration and production of hyperconcentrated mucus is a common feature of chronic obstructive lung diseases such as cystic fibrosis (CF) and chronic bronchitis (CB). Mucus hydration is driven by electrolyte transport activities, which in turn are regulated by airway epithelial purinergic receptors. The activity of these receptors is controlled by the extracellular concentrations of ATP and its metabolite adenosine. Vesicular and conducted pathways contribute to ATP release from airway epithelial cells. In this study, we review the evidence leading to the identification of major components of these pathways: (a) the vesicular nucleotide transporter VNUT (the product of the SLC17A9 gene), the ATP transporter mediating ATP storage in (and release from) mucin granules and secretory vesicles; and (b) the ATP conduit pannexin 1 expressed in non-mucous airway epithelial cells. We further illustrate that ablation of pannexin 1 reduces, at least in part, airway surface liquid (ASL) volume production, ciliary beating, and MCC rates.
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