Tagawa Maki, Yumoto Ryoko, Oda Keisuke, Nagai Junya, Takano Mikihisa
Department of Pharmaceutics and Therapeutics, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
Drug Metab Pharmacokinet. 2008;23(5):318-27. doi: 10.2133/dmpk.23.318.
FITC-albumin uptake by cultured alveolar type II epithelial cells, RLE-6TN, is mediated by high- and low-affinity transport systems. In this study, characteristics of the low-affinity transport system were evaluated. The uptake of FITC-albumin was time and temperature dependent and was inhibited by metabolic inhibitors and bafilomycin A1. Confocal laser scanning microscopic analysis showed punctate localization of the fluorescence in the cells, which was partly localized in lysosomes. FITC-albumin taken up by the cells gradually degraded over time, as shown by fluoroimage analyzer after SDS-PAGE. The uptake of FITC-albumin by RLE-6TN cells was not inhibited by caveolae-mediated endocytosis inhibitors such as nystatin, but was inhibited by clathrin-mediated endocytosis inhibitors such as phenylarsine oxide. The uptake was also inhibited by potassium depletion and hypertonicity, conditions known to inhibit clathrin-mediated endocytosis. In addition, macropinocytosis inhibitors such as 5-(N-ethyl-N-isopropyl) amiloride inhibited the uptake. These results indicate that the low-affinity transport of FITC-albumin in RLE-6TN cells is at least in part mediated by clathrin-mediated endocytosis, but not by caveolae-mediated endocytosis. Possible involvement of macropinocytosis was also suggested.
培养的肺泡II型上皮细胞RLE-6TN对异硫氰酸荧光素标记的白蛋白(FITC-白蛋白)的摄取由高亲和力和低亲和力转运系统介导。在本研究中,对低亲和力转运系统的特性进行了评估。FITC-白蛋白的摄取具有时间和温度依赖性,并受到代谢抑制剂和巴弗洛霉素A1的抑制。共聚焦激光扫描显微镜分析显示细胞内荧光呈点状定位,部分定位于溶酶体中。如SDS-PAGE后荧光图像分析仪所示,细胞摄取的FITC-白蛋白随时间逐渐降解。制霉菌素等小窝介导的内吞作用抑制剂不抑制RLE-6TN细胞对FITC-白蛋白的摄取,但苯砷氧化物等网格蛋白介导的内吞作用抑制剂可抑制其摄取。钾离子耗竭和高渗状态(已知可抑制网格蛋白介导的内吞作用)也可抑制摄取。此外,5-(N-乙基-N-异丙基)氨氯吡咪等巨胞饮作用抑制剂可抑制摄取。这些结果表明,RLE-6TN细胞中FITC-白蛋白的低亲和力转运至少部分由网格蛋白介导的内吞作用介导,而非小窝介导的内吞作用。也提示了巨胞饮作用可能参与其中。