Division of Biomedical Sciences St George's, University of London, London, UK.
Eur Respir J. 2012 Nov;40(5):1269-76. doi: 10.1183/09031936.00052612. Epub 2012 Aug 9.
For over 50 years, glucose has been recognised to cross the lung epithelial barrier and be transported by lung epithelial cells. However, until recently, research into these processes focused on their effects on lung liquid volume. Here, we consider a newly identified role for pulmonary glucose transport in maintaining low airway surface liquid (ASL) glucose concentrations and propose that this contributes to lung defence against infection. Glucose diffuses into ASL via paracellular pathways at a rate determined by paracellular permeability and the transepithelial glucose gradient. Glucose is removed from ASL in proximal airways via facilitative glucose transporters, down a concentration gradient generated by intracellular glucose metabolism. In the distal lung, glucose transport via sodium-coupled glucose transporters predominates. These processes vary between species but universally maintain ASL glucose at 3-20-fold lower concentrations than plasma. ASL glucose concentrations are increased in respiratory disease and by hyperglycaemia. Elevated ASL glucose in intensive care patients was associated with increased Staphylococcus aureus infection. Diabetic patients with and without chronic lung disease are at increased risk of respiratory infection. Understanding of mechanisms underlying lung glucose homeostasis could identify new therapeutic targets for control of ASL glucose and prevention and treatment of lung infection.
五十多年来，人们已经认识到葡萄糖可以穿过肺上皮屏障，并被肺上皮细胞转运。然而，直到最近，这些过程的研究才集中在它们对肺液量的影响上。在这里，我们考虑了肺葡萄糖转运的一个新的作用，即在维持低气道表面液（ASL）葡萄糖浓度方面的作用，并提出这有助于肺部抵抗感染。葡萄糖通过细胞旁途径扩散到 ASL 中，扩散速度由细胞旁通透性和跨上皮葡萄糖梯度决定。葡萄糖通过易化葡萄糖转运体从近气道中的 ASL 中被清除，这是由细胞内葡萄糖代谢产生的浓度梯度驱动的。在远端肺部，钠偶联葡萄糖转运体主导葡萄糖转运。这些过程在不同物种之间有所不同，但普遍使 ASL 中的葡萄糖浓度比血浆低 3-20 倍。呼吸疾病和高血糖会增加 ASL 中的葡萄糖浓度。重症监护患者的 ASL 葡萄糖升高与金黄色葡萄球菌感染增加有关。患有和不患有慢性肺部疾病的糖尿病患者患呼吸道感染的风险增加。对肺葡萄糖稳态机制的理解可以确定控制 ASL 葡萄糖以及预防和治疗肺部感染的新治疗靶点。
