OCTN2-Mediated Acetyl-<span style="font-variant: small-caps">l</span>-Carnitine Transport in Human Pulmonary Epithelial Cells In Vitro
Johanna J. Salomon,
Julia C. Gausterer,
Mohammed Ali Selo,
Ken-ichi Hosoya,
Hanno Huwer,
Nicole Schneider-Daum,
Claus-Michael Lehr,
Carsten Ehrhardt
Affiliations
Johanna J. Salomon
Department of Translational Pulmonology, Translational Lung Research Center (TLRC), Member of the German Center for Lung Research (DZL), University of Heidelberg, 69120 Heidelberg, Germany
Julia C. Gausterer
School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
Mohammed Ali Selo
School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
Ken-ichi Hosoya
Department of Pharmaceutics, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama 930-0194, Japan
Hanno Huwer
Department of Cardiothoracic Surgery, Völklingen Heart Centre, 66333 Völklingen, Germany
Nicole Schneider-Daum
Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, 66123 Saarbrücken, Germany
Claus-Michael Lehr
Drug Delivery, Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), Helmholtz Centre for Infection Research, 66123 Saarbrücken, Germany
Carsten Ehrhardt
School of Pharmacy and Pharmaceutical Sciences and Trinity Biomedical Sciences Institute, Trinity College Dublin, Dublin 2, Ireland
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 [3H]-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.