Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia

Muraglia Katrina A.; Chorghade Rajeev S.; Kim Bo Ram; Tang Xiao Xiao; Shah Viral S.; Grillo Anthony S.; Daniels Page N.; Cioffi Alexander G.; Karp Philip H.; Zhu Lingyang; Welsh Michael J.; Burke Martin D.

首页> 外文期刊>Nature >Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia

【24h】

Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia

机译：小分子离子通道增强了囊性纤维化气道上皮细胞的宿主防御能力

获取原文

获取原文并翻译 | 示例

掌桥外文数据库（机构版） >>

开具论文收录证明 >>

文献代查 >>

页面导航

摘要
著录项
相似文献
相关主题

摘要

Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO3- and Cl- secretion, reduce airway surface liquid pH, and impair respiratory host defences in people with cystic fibrosis(1-3). Here we report that apical addition of amphotericin B, a small molecule that forms unselective ion channels, restored HCO3- secretion and increased airway surface liquid pH in cultured airway epithelia from people with cystic fibrosis. These effects required the basolateral Na+, K+-ATPase, indicating that apical amphotericin B channels functionally interfaced with this driver of anion secretion. Amphotericin B also restored airway surface liquid pH, viscosity, and antibacterial activity in primary cultures of airway epithelia from people with cystic fibrosis caused by different mutations, including ones that do not yield CFTR, and increased airway surface liquid pH in CFTR-null pigs in vivo. Thus, unselective small-molecule ion channels can restore host defences in cystic fibrosis airway epithelia via a mechanism that is independent of CFTR and is therefore independent of genotype.

机译：囊性纤维化跨膜电导调节器（CFTR）的功能丧失突变会损害上皮HCO3-和Cl-分泌，降低气道表面液pH值，并损害囊性纤维化患者的呼吸道宿主防御能力（1-3）。在这里，我们报道了顶端添加的两性霉素B，这是一种形成非选择性离子通道的小分子，可从囊性纤维化患者的气道上皮中恢复HCO3-的分泌并增加气道表面液的pH值。这些作用需要基底外侧的Na +，K + -ATPase，这表明顶端的两性霉素B通道在功能上与这种阴离子分泌驱动因子相互作用。两性霉素B还恢复了由不同突变引起的囊性纤维化患者的气道上皮原代培养物的气道表面液pH值，粘度和抗菌活性，包括那些不产生CFTR的突变，并增加了CFTR无效猪的气道表面液pH值。体内。因此，非选择性小分子离子通道可以通过独立于CFTR并因此独立于基因型的机制恢复囊性纤维化气道上皮中的宿主防御。

著录项

来源
《Nature》 |2019年第7748期|405-408|共4页
作者
Muraglia Katrina A.; Chorghade Rajeev S.; Kim Bo Ram; Tang Xiao Xiao; Shah Viral S.; Grillo Anthony S.; Daniels Page N.; Cioffi Alexander G.; Karp Philip H.; Zhu Lingyang; Welsh Michael J.; Burke Martin D.;
展开▼
作者单位

Univ Illinois, Dept Biochem, Urbana, IL 61820 USA;

Univ Illinois, Dept Chem, Urbana, IL 61820 USA;

Univ Iowa, Dept Internal Med, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA|Univ Iowa, HHMI, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA;

Univ Iowa, Dept Internal Med, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA|Univ Iowa, HHMI, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA;

Univ Iowa, Dept Internal Med, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA|Univ Iowa, HHMI, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA;

Univ Illinois, Dept Chem, Urbana, IL 61820 USA;

Univ Illinois, Dept Biochem, Urbana, IL 61820 USA;

Univ Illinois, Dept Biochem, Urbana, IL 61820 USA;

Univ Iowa, Dept Internal Med, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA|Univ Iowa, HHMI, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA;

Univ Illinois, Dept Chem, Urbana, IL 61820 USA;

Univ Iowa, Dept Internal Med, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA 52242 USA|Univ Iowa, HHMI, Pappajohn Biomed Inst, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA|Univ Iowa, Dept Mol Physiol & Biophys, Roy J & Lucille A Carver Coll Med, Iowa City, IA USA;

Univ Illinois, Dept Biochem, Urbana, IL 61820 USA|Univ Illinois, Dept Chem, Urbana, IL 61820 USA|Univ Illinois, Carle Illinois Coll Med, Champaign, IL 61820 USA|Univ Illinois, Carl R Woese Inst Genom Biol, Champaign, IL 61820 USA|Univ Illinois, Beckman Inst Adv Sci & Technol, Champaign, IL 61820 USA;

展开▼
收录信息美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
原文格式 PDF
正文语种 eng
中图分类
关键词

相似文献

外文文献
中文文献
专利

1. Modulation of Ca2|[plus]|-Activated Cl|[minus]| Secretion by Basolateral K|[plus]| Channels in Human Normal and Cystic Fibrosis Airway Epithelia [J] . Marcus Mall, Tanja Gonska, J?rg Thomas, Pediatric Research . 2003,第4期

机译：Ca2 | [正] |活化的Cl | [负] |的调节基底外侧K | [加] |的分泌人正常和囊性纤维化气道上皮细胞的通道
2. Mutating the Conserved Q-loop Glutamine 1291 Selectively Disrupts Adenylate Kinase-dependent Channel Gating of the ATP-binding Cassette (ABC) Adenylate Kinase Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) and Reduces Channel Function in Primary Human Airway Epithelia * [J] . Qian Dong, Sarah E. Ernst, Lynda S. Ostedgaard, The Journal of biological chemistry . 2015,第22期

机译：突变保守的Q环谷胺1291选择性地破坏ATP结合盒（ABC）腺苷酸激酶囊性纤维化纤维化纤维化纤维化纤维化纤维化纤维化造型调节器（CFTR）的腺苷酸激酶依赖性通道栅极，并减少初级人气道上皮的信道功能 *
3. Loss of CFTR chloride channels alters salt absorption by cystic fibrosis airway epithelia in vitro. [J] . Zabner J, Smith JJ, Karp PH, Molecular cell . 1998,第3期

机译：CFTR氯离子通道的丢失会在体外改变囊性纤维化气道上皮的盐吸收。
4. Population proteome investigation of Pseudomonas aeruginosa clinical isolates collected from cystic fibrosis patient airways [C] . Xia Wu, Benjamin J. Staudinger, Jayanthi Garudathri, ASMS Conference on Mass Spectrometry and Allied Topics . 2015

机译：从囊性纤维化患者气道中收集的假单胞菌铜绿假单胞菌临床分离物的人口蛋白质组
5. Interactions between Pseudomonas aeruginosa and airway epithelia in cystic fibrosis [D] . Hybiske, Kevin James 2003

机译：铜绿假单胞菌与气道上皮细胞在囊性纤维化中的相互作用
6. Small molecule ion channels increase host defenses in cystic fibrosis airway epithelia [O] . Katrina A. Muraglia, Rajeev S. Chorghade, Bo Ram Kim, -1

机译：小分子离子通道增强了囊性纤维化气道上皮细胞的宿主防御能力
7. Modulation of Ca2+-Activated Cl− Secretion by Basolateral K+ Channels in Human Normal and Cystic Fibrosis Airway Epithelia [O] . Marcus Mall, Tanja Gonska, Jörg Thomas, 2003

机译：通过Basolateral K +通道的Ca 2 +活化的Cl-分泌的调节患者正常和囊性纤维化通道上皮细胞

Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia

摘要

著录项

相似文献

相关主题

期刊订阅