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Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.

dc.contributor.author St John, AL
dc.contributor.author Rathore, AP
dc.contributor.author Raghavan, B
dc.contributor.author Ng, ML
dc.contributor.author Abraham, SN
dc.coverage.spatial England
dc.date.accessioned 2016-07-15T15:04:26Z
dc.date.issued 2013-04-30
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/23638300
dc.identifier 00481
dc.identifier.uri http://hdl.handle.net/10161/12468
dc.description.abstract Dengue Virus (DENV), a flavivirus spread by mosquito vectors, can cause vascular leakage and hemorrhaging. However, the processes that underlie increased vascular permeability and pathological plasma leakage during viral hemorrhagic fevers are largely unknown. Mast cells (MCs) are activated in vivo during DENV infection, and we show that this elevates systemic levels of their vasoactive products, including chymase, and promotes vascular leakage. Treatment of infected animals with MC-stabilizing drugs or a leukotriene receptor antagonist restores vascular integrity during experimental DENV infection. Validation of these findings using human clinical samples revealed a direct correlation between MC activation and DENV disease severity. In humans, the MC-specific product, chymase, is a predictive biomarker distinguishing dengue fever (DF) and dengue hemorrhagic fever (DHF). Additionally, our findings reveal MCs as potential therapeutic targets to prevent DENV-induced vasculopathy, suggesting MC-stabilizing drugs should be evaluated for their effectiveness in improving disease outcomes during viral hemorrhagic fevers. DOI:http://dx.doi.org/10.7554/eLife.00481.001.
dc.language eng
dc.relation.ispartof Elife
dc.relation.isversionof 10.7554/eLife.00481
dc.subject Human
dc.subject Mouse
dc.subject Viruses
dc.subject chymase
dc.subject dengue virus
dc.subject leukotrienes
dc.subject mast cell
dc.subject vascular leakage
dc.subject Animals
dc.subject Capillary Permeability
dc.subject Chymases
dc.subject Dengue Virus
dc.subject Leukotrienes
dc.subject Mast Cells
dc.subject Mice
dc.title Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.
dc.type Journal article
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/23638300
pubs.begin-page e00481
pubs.organisational-group Basic Science Departments
pubs.organisational-group Clinical Science Departments
pubs.organisational-group Duke
pubs.organisational-group Duke Cancer Institute
pubs.organisational-group Immunology
pubs.organisational-group Institutes and Centers
pubs.organisational-group Molecular Genetics and Microbiology
pubs.organisational-group Pathology
pubs.organisational-group School of Medicine
pubs.publication-status Published online
pubs.volume 2


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