Elevated paracellular glucose flux across cystic fibrosis airway epithelial monolayers is an important factor for Pseudomonas aeruginosa growth.
Elevated paracellular glucose flux across cystic fibrosis airway epithelial monolayers is an important factor for Pseudomonas aeruginosa growth.
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跨囊性纤维化气道上皮单层的细胞旁葡萄糖通量升高是铜绿假单胞菌生长的重要因素。
DOI：
10.1371/journal.pone.0076283
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Baines DL
中科院分区：
文献类型：
--
作者：
Garnett JP;Gray MA;Tarran R;Brodlie M;Ward C;Baker EH;Baines DL
患有囊性纤维化(CF)并发展为相关性糖尿病(CFRD)的人会加速肺功能衰退，增加耐药铜绿假单胞菌感染，并增加肺部恶化。我们之前已经证明，CFRD患者的呼吸道表面液体(ASL)中的葡萄糖浓度升高，尤其是在CFRD患者。因此，我们探讨了这样的假设，即CF气道上皮细胞的葡萄糖动态平衡被改变，进入ASL的葡萄糖流量的增加促进了细菌的生长，其影响超过了其他与囊性纤维化跨膜传导调节因子(CFTR)相关的ASL异常。本研究的目的是比较在正常条件下和在Ps存在的情况下，CF型和非CF型原代人支气管上皮(HBE)单层中调节呼吸道葡萄糖稳态的机制。铜绿假单胞菌滤液。在5 mM或15 mM葡萄糖存在的情况下进行HBe-细菌共培养，以研究血糖的变化，如CFRD中所见的血糖变化，如何影响管腔内的P。铜绿假单胞菌生长。用CALU-3细胞单层来评价葡萄糖对Ps的潜在重要性。铜绿假单胞菌的生长，与CFASL的其他特征相比，即粘液高粘度和依赖CFTR的液体分泌受损。我们发现，基底侧葡萄糖的升高促进了Ps的顶端生长。CF上皮单分子层上的铜绿假单胞菌多于非CF上皮单层。PS。与非CF单分子层相比，铜绿假单胞菌分泌物诱导更多的葡萄糖通过CF型呼吸道上皮单分子层，我们认为这增加了ASL中葡萄糖的利用率，有利于细菌的生长。此外，升高基底侧位血糖增加了Ps。在CALU-3呼吸道上皮细胞-细菌共培养中，铜绿假单胞菌的生长超过任何CFTR依赖效应以及粘液的存在或不存在。总之，这些研究强调了葡萄糖作为促进Ps的另一个因素的重要性。铜绿假单胞菌的生长与CF病的呼吸道感染
People with cystic fibrosis (CF) who develop related diabetes (CFRD) have accelerated pulmonary decline, increased infection with antibiotic-resistant Pseudomonas aeruginosa and increased pulmonary exacerbations. We have previously shown that glucose concentrations are elevated in airway surface liquid (ASL) of people with CF, particularly in those with CFRD. We therefore explored the hypotheses that glucose homeostasis is altered in CF airway epithelia and that elevation of glucose flux into ASL drives increased bacterial growth, with an effect over and above other cystic fibrosis transmembrane conductance regulator (CFTR)-related ASL abnormalities. The aim of this study was to compare the mechanisms governing airway glucose homeostasis in CF and non-CF primary human bronchial epithelial (HBE) monolayers, under normal conditions and in the presence of Ps. aeruginosa filtrate. HBE-bacterial co-cultures were performed in the presence of 5 mM or 15 mM basolateral glucose to investigate how changes in blood glucose, such as those seen in CFRD, affects luminal Ps. aeruginosa growth. Calu-3 cell monolayers were used to evaluate the potential importance of glucose on Ps. aeruginosa growth, in comparison to other hallmarks of the CF ASL, namely mucus hyperviscosity and impaired CFTR-dependent fluid secretions. We show that elevation of basolateral glucose promotes the apical growth of Ps. aeruginosa on CF airway epithelial monolayers more than non-CF monolayers. Ps. aeruginosa secretions elicited more glucose flux across CF airway epithelial monolayers compared to non-CF monolayers which we propose increases glucose availability in ASL for bacterial growth. In addition, elevating basolateral glucose increased Ps. aeruginosa growth over and above any CFTR-dependent effects and the presence or absence of mucus in Calu-3 airway epithelia-bacteria co-cultures. Together these studies highlight the importance of glucose as an additional factor in promoting Ps. aeruginosa growth and respiratory infection in CF disease.
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DOI：
10.1164/rccm.200207-765oc
发表时间：
2004-03-01
影响因子：
24.7
作者：
Becker, MN;Sauer, MS;Randell, SH
通讯作者：
Randell, SH
影响因子：
3.7
作者：
Pezzulo AA;Gutiérrez J;Duschner KS;McConnell KS;Taft PJ;Ernst SE;Yahr TL;Rahmouni K;Klesney-Tait J;Stoltz DA;Zabner J
通讯作者：
Zabner J
影响因子：
4.8
作者：
Garnett, James P.;Hickman, Emma;Gray, Michael A.
通讯作者：
Gray, Michael A.
DOI：
10.1007/978-1-61779-120-8_18
发表时间：
2011-01-01
期刊：
CYSTIC FIBROSIS: DIAGNOSIS AND PROTOCOLS, VOL II: METHODS AND RESOURCES TO UNDERSTAND CYSTIC FIBROSIS
影响因子：
--
作者：
Randell, Scott H.;Fulcher, M. Leslie;Olsen, John C.
通讯作者：
Olsen, John C.
影响因子：
5.2
作者：
Brennan, Amanda L.;Gyi, Khin M.;Baker, Emma H.
通讯作者：
Baker, Emma H.