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• W2581171482 abstract "Rationale: The transport of interstitial fluid and solutes into lymphatic vessels is important for maintaining interstitial homeostasis and delivering antigens and soluble factors to the lymph node for immune surveillance. Transendothelial transport across lymphatic endothelial cells (LECs) is commonly considered to occur paracellularly, or between cell–cell junctions, and driven by local pressure and concentration gradients. However, emerging evidence suggests that LECs also play active roles in regulating interstitial solute balance and can scavenge and store antigens, raising the possibility that vesicular or transcellular pathways may be important in lymphatic solute transport. Objective: The aim of this study was to determine the relative importance of transcellular (vesicular) versus paracellular transport pathways by LECs and how mechanical stress (ie, fluid flow conditioning) alters either pathway. Methods and Results: We demonstrate that transcellular transport mechanisms substantially contribute to lymphatic solute transport and that solute uptake occurs in both caveolae- and clathrin-coated vesicles. In vivo, intracelluar uptake of fluorescently labeled albumin after intradermal injection by LECs was similar to that of dermal dendritic cells. In vitro, we developed a method to differentially quantify intracellular solute uptake versus transendothelial transport by LECs. LECs preconditioned to 1 µm/s transmural flow demonstrated increased uptake and basal-to-apical solute transport, which could be substantially reversed by blocking dynamin-dependent vesicle formation. Conclusions: These findings reveal the importance of intracellular transport in steady-state lymph formation and suggest that LECs use transcellular mechanisms in parallel to the well-described paracellular route to modulate solute transport from the interstitium according to biomechanical cues." @default.
• W2581171482 created "2017-02-03" @default.
• W2581171482 creator A5024837241 @default.
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• W2581171482 creator A5048232627 @default.
• W2581171482 creator A5088336448 @default.
• W2581171482 creator A5088767177 @default.
• W2581171482 date "2017-04-28" @default.
• W2581171482 modified "2023-10-10" @default.
• W2581171482 title "Transcellular Pathways in Lymphatic Endothelial Cells Regulate Changes in Solute Transport by Fluid Stress" @default.
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• W2581171482 doi "https://doi.org/10.1161/circresaha.116.309828" @default.
• W2581171482 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28130294" @default.
• W2581171482 hasPublicationYear "2017" @default.
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