Johnson Meshell, Allen Lennell, Dobbs Leland
Department of Medicine, University of California, San Francisco, 3333 California St., Suite 150, Box 1245, San Francisco, CA 94118, USA.
Am J Physiol Lung Cell Mol Physiol. 2009 Nov;297(5):L816-27. doi: 10.1152/ajplung.90466.2008. Epub 2009 Aug 14.
Although Cl- transport in fetal lung is important for fluid secretion and normal lung development, the role of Cl- transport in adult lung is not well understood. In physiological studies, the cystic fibrosis transmembrane regulator (CFTR) plays a role in fluid absorption in the distal air spaces of adult lung, and alveolar type II cells cultured for 5 days have the capacity to transport Cl-. Although both alveolar type I and type II cells express CFTR, it has previously not been known whether type I cells transport Cl-. We studied Cl- uptake in isolated type I cells directly, using either radioisotopic tracers or halide-sensitive fluorescent indicators. By both methods, type I cells take up Cl-. In the presence of beta-adrenergic agonist stimulation, Cl- uptake can be inhibited by CFTR antagonists. Type I cells express both the Cl-/HCO3- anion exchanger AE2 and the voltage-gated Cl- channels CLC5 and CLC2. Inhibitors of AE2 also block Cl- uptake in type I cells. Together, these results demonstrate that type I cells are capable of Cl- uptake and suggest that the effects seen in whole lung studies establishing the importance of Cl- movement in alveolar fluid clearance may be, in part, the result of Cl- transport across type I cells.
尽管氯离子（Cl⁻）转运在胎儿肺中对液体分泌和正常肺发育很重要，但Cl⁻转运在成年肺中的作用尚未得到充分了解。在生理学研究中，囊性纤维化跨膜传导调节因子（CFTR）在成年肺远端气腔的液体吸收中起作用，培养5天的II型肺泡细胞具有转运Cl⁻的能力。尽管I型和II型肺泡细胞都表达CFTR，但此前尚不清楚I型细胞是否转运Cl⁻。我们使用放射性同位素示踪剂或卤化物敏感荧光指示剂直接研究分离的I型细胞中的Cl⁻摄取。通过这两种方法，I型细胞都摄取Cl⁻。在β-肾上腺素能激动剂刺激下，CFTR拮抗剂可抑制Cl⁻摄取。I型细胞表达Cl⁻/HCO₃⁻阴离子交换蛋白AE2以及电压门控Cl⁻通道CLC5和CLC2。AE2抑制剂也会阻断I型细胞中的Cl⁻摄取。总之，这些结果表明I型细胞能够摄取Cl⁻，并表明在确定Cl⁻运动在肺泡液体清除中的重要性的全肺研究中所观察到的效应可能部分是Cl⁻跨I型细胞转运的结果。
