Salomon Johanna J, Gausterer Julia C, Selo Mohammed Ali, Hosoya Ken-Ichi, Huwer Hanno, Schneider-Daum Nicole, Lehr Claus-Michael, Ehrhardt Carsten
Department of Translational Pulmonology, Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, 69120 Heidelberg, Germany.
School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland.
Pharmaceutics. 2019 Aug 7;11(8):396. doi: 10.3390/pharmaceutics11080396.
The carnitine transporter OCTN2 is associated with asthma and other inflammatory diseases. The aims of this work were (i) to determine carnitine uptake into freshly isolated human alveolar type I (ATI)-like epithelial cells in primary culture, (ii) to compare the kinetics of carnitine uptake between respiratory epithelial in vitro cell models, and (iii) to establish whether any cell line was a suitable model for studies of carnitine transport at the air-blood barrier. Levels of time-dependent [H]-acetyl-l-carnitine uptake were similar in ATI-like, NCl-H441, and Calu-3 epithelial cells, whereas uptake into A549 cells was ~5 times higher. Uptake inhibition was more pronounced by OCTN2 modulators, such as l-Carnitine and verapamil, in ATI-like primary epithelial cells compared to NCl-H441 and Calu-3 epithelial cells. Our findings suggest that OCTN2 is involved in the cellular uptake of acetyl-l-carnitine at the alveolar epithelium and that none of the tested cell lines are optimal surrogates for primary cells.
肉碱转运体OCTN2与哮喘及其他炎症性疾病相关。本研究的目的是：（i）测定原代培养的新鲜分离的人I型肺泡（ATI）样上皮细胞对肉碱的摄取；（ii）比较体外呼吸道上皮细胞模型之间肉碱摄取的动力学；（iii）确定是否有任何细胞系是研究气血屏障处肉碱转运的合适模型。在ATI样、NCl-H441和Calu-3上皮细胞中，时间依赖性的[H]-乙酰左旋肉碱摄取水平相似，而A549细胞中的摄取量约高5倍。与NCl-H441和Calu-3上皮细胞相比，在ATI样原代上皮细胞中，OCTN2调节剂（如左旋肉碱和维拉帕米）对摄取的抑制作用更明显。我们的研究结果表明，OCTN2参与肺泡上皮细胞对乙酰左旋肉碱的摄取，且所测试的细胞系均不是原代细胞的最佳替代物。
