Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.
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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.
Published Version (Please cite this version)10.7554/eLife.00481
Publication InfoSt John, Ashley L; Rathore, Abhay PS; Raghavan, Bhuvanakantham; Ng, Mah-Lee; & Abraham, Soman N (2013). Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife, 2. pp. e00481. 10.7554/eLife.00481. Retrieved from https://hdl.handle.net/10161/12468.
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Soman Ninan Abraham
Grace Kerby Distinguished Professor of Pathology
The Abraham laboratory is interested in developing innovative approaches for curbing microbial infections through the study of the molecular interactions occurring between pathogenic bacteria and prominent immune and epithelial cells. We believe that there is a significant amount of crosstalk occurring between bacteria and host cells during infection and that the outcome of this interaction dictates both how quickly the infection is cleared and the severity of the pathology associated with th
Ashley St John
Adjunct Associate Professor in the Department of Pathology
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