Demonstration of ATP-dependent, transcellular transport of lipid across the lymphatic endothelium using an in vitro model of the lacteal.
Demonstration of ATP-dependent, transcellular transport of lipid across the lymphatic endothelium using an in vitro model of the lacteal.
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DOI：
10.1007/s11095-013-1218-x
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发表时间：
2013-12
影响因子：
3.7
通讯作者：
Dixon, J. Brandon
中科院分区：
文献类型：
--
作者：
Reed, Alana L.;Rowson, Sydney A.;Dixon, J. Brandon
淋巴系统在组织液平衡、免疫细胞运输和从肠道摄取膳食脂质方面起着至关重要的作用。鉴于这些作用，人们对通过口服脂基制剂或皮内给药来靶向淋巴系统产生了兴趣。然而，淋巴管对脂质摄取的调节机制尚不清楚。因此，我们试图修改先前开发的体外模型，以研究ATP在脂质摄取到淋巴管中的作用。在transwell膜上培养淋巴内皮细胞，计算存在或不存在atp抑制剂叠氮化钠时，对游离脂肪酸和Caco-2细胞分泌脂质的有效通透性。结果：ATP抑制降低Caco-2细胞分泌的脂质转运，但不影响葡聚糖转运。在atp抑制的早期阶段，FFA转运主要依赖于atp，而Caco-2细胞分泌的脂质转运在研究的所有时间点都降低。此外，转运的跨细胞成分高度依赖于atp，这一机制在成纤维细胞中未观察到，表明这些机制是淋巴管独有的。通过ATP抑制，Caco-2细胞分泌的脂质总转运量呈剂量依赖性降低，而跨细胞脂蛋白转运完全减弱。脂质通过淋巴内皮的运输，正如这个体外模型所证明的那样，部分是通过atp依赖的、独立于被动通透性的跨细胞途径发生的。这一机制在体内存在的程度仍有待确定，未来的工作应在这一领域进行。
The lymphatic system plays crucial roles in tissue fluid balance, trafficking of immune cells, and the uptake of dietary lipid from the intestine. Given these roles there has been an interest in targeting lymphatics through oral lipid-based formulations or intradermal delivery of drug carrier systems. However the mechanisms regulating lipid uptake by lymphatics remain unknown. Thus we sought to modify a previously developed in vitro model to investigate the role of ATP in lipid uptake into the lymphatics. Lymphatic endothelial cells were cultured on a transwell membrane and the effective permeability to free fatty acid and Caco-2 cell-secreted lipid was calculated in the presence or absence of the ATP-inhibitor sodium azide. Results: ATP inhibition reduced Caco-2 cell-secreted lipid transport, but not dextran transport. FFA transport was ATP-dependent primarily during early periods of ATP-inhibition, while Caco-2 cell-secreted lipid transport was lowered at all time points studied. Furthermore, the transcellular component of transport was highly ATP-dependent, a mechanism not observed in fibroblasts, suggesting these mechanisms are unique to lymphatics. Total transport of Caco-2 cell-secreted lipid was dose-dependently reduced by ATP inhibition, and transcellular lipoprotein transport was completely attenuated. The transport of lipid across the lymphatic endothelium as demonstrated with this in vitro model occurs in part by an ATP-dependent, transcellular route independent of passive permeability. It remains to be determined the extent that this mechanism exists in vivo and future work should be directed in this area.
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影响因子：
14
作者：
Liu, Rong;Gilmore, Denis M.;Zubris, Kimberly Ann V.;Xu, Xiaoyin;Catalano, Paul J.;Padera, Robert F.;Grinstaff, Mark W.;Colson, Yolonda L.
通讯作者：
Colson, Yolonda L.
影响因子：
1.4
作者：
Ando, T.;Jordan, P.;Alexander, J. S.
通讯作者：
Alexander, J. S.
影响因子：
5.2
作者：
Dixon JB
通讯作者：
Dixon JB
影响因子：
4.8
作者：
Luchoomun, J;Hussain, MM
通讯作者：
Hussain, MM
影响因子：
3.8
作者：
Dixon, J. Brandon;Raghunathan, Sandeep;Swartz, Melody A.
通讯作者：
Swartz, Melody A.