Glucose depletion in the airway surface liquid is essential for sterility of the airways.
Glucose depletion in the airway surface liquid is essential for sterility of the airways.
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DOI：
10.1371/journal.pone.0016166
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发表时间：
2011-01-20
期刊：
影响因子：
3.7
通讯作者：
Zabner J
中科院分区：
文献类型：
--
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
糖尿病使宿主易受细菌感染。此外，高血糖症已被证明是呼吸道感染的独立危险因素。气道上皮细胞的腔表面被一层薄薄的气道表面液体（ASL）覆盖，尽管持续暴露于细菌，但通常是无菌的。气道中细菌生长和杀灭之间的平衡决定了暴露于吸入或吸出细菌的结果：感染或不育。我们假设限制ASL中的碳源（包括葡萄糖）是肺无菌所必需的。我们发现气道上皮细胞通过一种新的机制消耗ASL中的葡萄糖，该机制涉及GLUT-1和GLUT-10的极化表达、细胞内葡萄糖磷酸化以及在分化良好的人气道上皮细胞培养物和从人气管切除的气道上皮细胞片段中的相对细胞旁葡萄糖渗透性较低。此外，我们发现ASL中葡萄糖浓度的增加增强了体外铜绿假单胞菌的生长以及体内高血糖ob/ob和db/db小鼠肺中铜绿假单胞菌的生长。相反，高血糖对不能利用葡萄糖作为碳源的铜绿假单胞菌突变体的肺内细菌生长没有影响。我们的数据表明，在气道上皮细胞表面的葡萄糖消耗是一种新的机制，先天免疫。这种机制对于气道的无菌性是重要的，并且在高血糖症和导致肺中上皮屏障破坏的病症中具有意义。
Diabetes mellitus predisposes the host to bacterial infections. Moreover, hyperglycemia has been shown to be an independent risk factor for respiratory infections. The luminal surface of airway epithelia is covered by a thin layer of airway surface liquid (ASL) and is normally sterile despite constant exposure to bacteria. The balance between bacterial growth and killing in the airway determines the outcome of exposure to inhaled or aspirated bacteria: infection or sterility. We hypothesized that restriction of carbon sources –including glucose– in the ASL is required for sterility of the lungs. We found that airway epithelia deplete glucose from the ASL via a novel mechanism involving polarized expression of GLUT-1 and GLUT-10, intracellular glucose phosphorylation, and low relative paracellular glucose permeability in well-differentiated cultures of human airway epithelia and in segments of airway epithelia excised from human tracheas. Moreover, we found that increased glucose concentration in the ASL augments growth of P. aeruginosa in vitro and in the lungs of hyperglycemic ob/ob and db/db mice in vivo. In contrast, hyperglycemia had no effect on intrapulmonary bacterial growth of a P. aeruginosa mutant that is unable to utilize glucose as a carbon source. Our data suggest that depletion of glucose in the airway epithelial surface is a novel mechanism for innate immunity. This mechanism is important for sterility of the airways and has implications in hyperglycemia and conditions that result in disruption of the epithelial barrier in the lung.
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影响因子：
3.2
作者：
De Groot, A;Koster, M;Filloux, A
通讯作者：
Filloux, A
影响因子：
4.5
作者：
Kalsi, Kameljit K.;Baker, Emma H.;Baines, Deborah L.
通讯作者：
Baines, Deborah L.
影响因子：
5.2
作者：
Brennan, Amanda L.;Gyi, Khin M.;Baker, Emma H.
通讯作者：
Baker, Emma H.
影响因子：
--
作者：
Bento, JL;Bowden, DW;Segade, F
通讯作者：
Segade, F
DOI：
10.1073/pnas.2036282100
发表时间：
2003-11-25
影响因子：
11.1
作者：
Jacobs, MA;Alwood, A;Manoil, C
通讯作者：
Manoil, C