Platelet activating factor contributes to vascular leak in acute dengue infection.
BACKGROUND:Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate it...
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ftdoajarticles:oai:doaj.org/article:cb67f478946d455d816bf8160ba6e506 2023-05-15T15:12:45+02:00 Platelet activating factor contributes to vascular leak in acute dengue infection. Chandima Jeewandara Laksiri Gomes N Wickramasinghe Danuta Gutowska-Owsiak Dominic Waithe S A Paranavitane N L A Shyamali Graham S Ogg Gathsaurie Neelika Malavige 2015-02-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0003459 https://doaj.org/article/cb67f478946d455d816bf8160ba6e506 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4315531?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003459 https://doaj.org/article/cb67f478946d455d816bf8160ba6e506 PLoS Neglected Tropical Diseases, Vol 9, Iss 2, p e0003459 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0003459 2022-12-31T12:25:13Z BACKGROUND:Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. MATERIALS AND METHODS:PAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs. RESULTS:PAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker. CONCLUSION:Our results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 2 e0003459 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Chandima Jeewandara Laksiri Gomes N Wickramasinghe Danuta Gutowska-Owsiak Dominic Waithe S A Paranavitane N L A Shyamali Graham S Ogg Gathsaurie Neelika Malavige Platelet activating factor contributes to vascular leak in acute dengue infection. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
BACKGROUND:Although plasma leakage is the hallmark of severe dengue infections, the factors that cause increased vascular permeability have not been identified. As platelet activating factor (PAF) is associated with an increase in vascular permeability in other diseases, we set out to investigate its role in acute dengue infection. MATERIALS AND METHODS:PAF levels were initially assessed in 25 patients with acute dengue infection to determine if they were increased in acute dengue. For investigation of the kinetics of PAF, serial PAF values were assessed in 36 patients. The effect of dengue serum on tight junction protein ZO-1 was determined by using human endothelial cell lines (HUVECs). The effect of dengue serum on and trans-endothelial resistance (TEER) was also measured on HUVECs. RESULTS:PAF levels were significantly higher in patients with acute dengue (n = 25; p = 0.001) when compared to healthy individuals (n = 12). In further investigation of the kinetics of PAF in serial blood samples of patients (n = 36), PAF levels rose just before the onset of the critical phase. PAF levels were significantly higher in patients with evidence of vascular leak throughout the course of the illness when compared to those with milder disease. Serum from patients with dengue significantly down-regulated expression of tight junction protein, ZO-1 (p = 0.004), HUVECs. This was significantly inhibited (p = 0.004) by use of a PAF receptor (PAFR) blocker. Serum from dengue patients also significantly reduced TEER and this reduction was also significantly (p = 0.02) inhibited by prior incubation with the PAFR blocker. CONCLUSION:Our results suggest the PAF is likely to be playing a significant role in inducing vascular leak in acute dengue infection which offers a potential target for therapeutic intervention. |
format |
Article in Journal/Newspaper |
author |
Chandima Jeewandara Laksiri Gomes N Wickramasinghe Danuta Gutowska-Owsiak Dominic Waithe S A Paranavitane N L A Shyamali Graham S Ogg Gathsaurie Neelika Malavige |
author_facet |
Chandima Jeewandara Laksiri Gomes N Wickramasinghe Danuta Gutowska-Owsiak Dominic Waithe S A Paranavitane N L A Shyamali Graham S Ogg Gathsaurie Neelika Malavige |
author_sort |
Chandima Jeewandara |
title |
Platelet activating factor contributes to vascular leak in acute dengue infection. |
title_short |
Platelet activating factor contributes to vascular leak in acute dengue infection. |
title_full |
Platelet activating factor contributes to vascular leak in acute dengue infection. |
title_fullStr |
Platelet activating factor contributes to vascular leak in acute dengue infection. |
title_full_unstemmed |
Platelet activating factor contributes to vascular leak in acute dengue infection. |
title_sort |
platelet activating factor contributes to vascular leak in acute dengue infection. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0003459 https://doaj.org/article/cb67f478946d455d816bf8160ba6e506 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 2, p e0003459 (2015) |
op_relation |
http://europepmc.org/articles/PMC4315531?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0003459 https://doaj.org/article/cb67f478946d455d816bf8160ba6e506 |
op_doi |
https://doi.org/10.1371/journal.pntd.0003459 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
2 |
container_start_page |
e0003459 |
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1766343388670459904 |