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Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever

Vascular leakage is a life-threatening complication of dengue virus (DENV) infection. Previously, association between “paracellular” endothelial hyperpermeability and plasma leakage had been extensively investigated. However, whether “transcellular” endothelial leakage is involved in dengue hemorrha...

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Autores principales: Chanthick, Chanettee, Kanlaya, Rattiyaporn, Kiatbumrung, Rattanaporn, Pattanakitsakul, Sa-nga, Thongboonkerd, Visith
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992822/
https://www.ncbi.nlm.nih.gov/pubmed/27546060
http://dx.doi.org/10.1038/srep31855
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author Chanthick, Chanettee
Kanlaya, Rattiyaporn
Kiatbumrung, Rattanaporn
Pattanakitsakul, Sa-nga
Thongboonkerd, Visith
author_facet Chanthick, Chanettee
Kanlaya, Rattiyaporn
Kiatbumrung, Rattanaporn
Pattanakitsakul, Sa-nga
Thongboonkerd, Visith
author_sort Chanthick, Chanettee
collection PubMed
description Vascular leakage is a life-threatening complication of dengue virus (DENV) infection. Previously, association between “paracellular” endothelial hyperpermeability and plasma leakage had been extensively investigated. However, whether “transcellular” endothelial leakage is involved in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) remained unknown. We thus investigated effects of DENV (serotype 2) infection on transcellular transport of albumin, the main oncotic plasma protein, through human endothelial cell monolayer by Western blotting, immunofluorescence staining, fluorescence imaging, and fluorometry. The data showed that Alexa488-conjugated bovine serum albumin (Alexa488-BSA) was detectable inside DENV2-infected cells and its level was progressively increased during 48-h post-infection. While paracellular transport could be excluded using FITC-conjugated dextran, Alexa488-BSA was progressively increased and decreased in lower and upper chambers of Transwell, respectively. Pretreatment with nystatin, an inhibitor of caveolae-dependent endocytic pathway, significantly decreased albumin internalization into the DENV2-infected cells, whereas inhibitors of other endocytic pathways showed no significant effects. Co-localization of the internalized Alexa488-BSA and caveolin-1 was also observed. Our findings indicate that DENV infection enhances caveolae-mediated albumin transcytosis through human endothelial cells that may ultimately induce plasma leakage from intravascular compartment. Further elucidation of this model in vivo may lead to effective prevention and better therapeutic outcome of DHF/DSS.
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spelling pubmed-49928222016-08-30 Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever Chanthick, Chanettee Kanlaya, Rattiyaporn Kiatbumrung, Rattanaporn Pattanakitsakul, Sa-nga Thongboonkerd, Visith Sci Rep Article Vascular leakage is a life-threatening complication of dengue virus (DENV) infection. Previously, association between “paracellular” endothelial hyperpermeability and plasma leakage had been extensively investigated. However, whether “transcellular” endothelial leakage is involved in dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) remained unknown. We thus investigated effects of DENV (serotype 2) infection on transcellular transport of albumin, the main oncotic plasma protein, through human endothelial cell monolayer by Western blotting, immunofluorescence staining, fluorescence imaging, and fluorometry. The data showed that Alexa488-conjugated bovine serum albumin (Alexa488-BSA) was detectable inside DENV2-infected cells and its level was progressively increased during 48-h post-infection. While paracellular transport could be excluded using FITC-conjugated dextran, Alexa488-BSA was progressively increased and decreased in lower and upper chambers of Transwell, respectively. Pretreatment with nystatin, an inhibitor of caveolae-dependent endocytic pathway, significantly decreased albumin internalization into the DENV2-infected cells, whereas inhibitors of other endocytic pathways showed no significant effects. Co-localization of the internalized Alexa488-BSA and caveolin-1 was also observed. Our findings indicate that DENV infection enhances caveolae-mediated albumin transcytosis through human endothelial cells that may ultimately induce plasma leakage from intravascular compartment. Further elucidation of this model in vivo may lead to effective prevention and better therapeutic outcome of DHF/DSS. Nature Publishing Group 2016-08-22 /pmc/articles/PMC4992822/ /pubmed/27546060 http://dx.doi.org/10.1038/srep31855 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Chanthick, Chanettee
Kanlaya, Rattiyaporn
Kiatbumrung, Rattanaporn
Pattanakitsakul, Sa-nga
Thongboonkerd, Visith
Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever
title Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever
title_full Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever
title_fullStr Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever
title_full_unstemmed Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever
title_short Caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: A model of vascular leakage in dengue hemorrhagic fever
title_sort caveolae-mediated albumin transcytosis is enhanced in dengue-infected human endothelial cells: a model of vascular leakage in dengue hemorrhagic fever
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4992822/
https://www.ncbi.nlm.nih.gov/pubmed/27546060
http://dx.doi.org/10.1038/srep31855
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