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

Publication ,  Journal Article
St John, AL; Rathore, APS; Raghavan, B; Ng, M-L; Abraham, SN
Published in: Elife
April 30, 2013

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.

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Published In

Elife

DOI

ISSN

2050-084X

Publication Date

April 30, 2013

Volume

2

Start / End Page

e00481

Location

England

Related Subject Headings

  • Mice
  • Mast Cells
  • Leukotrienes
  • Dengue Virus
  • Chymases
  • Capillary Permeability
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences
 

Citation

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St John, A. L., Rathore, A. P. S., Raghavan, B., Ng, M.-L., & Abraham, S. N. (2013). Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife, 2, e00481. https://doi.org/10.7554/eLife.00481
St John, Ashley L., Abhay P. S. Rathore, Bhuvanakantham Raghavan, Mah-Lee Ng, and Soman N. Abraham. “Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.Elife 2 (April 30, 2013): e00481. https://doi.org/10.7554/eLife.00481.
St John AL, Rathore APS, Raghavan B, Ng M-L, Abraham SN. Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife. 2013 Apr 30;2:e00481.
St John, Ashley L., et al. “Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage.Elife, vol. 2, Apr. 2013, p. e00481. Pubmed, doi:10.7554/eLife.00481.
St John AL, Rathore APS, Raghavan B, Ng M-L, Abraham SN. Contributions of mast cells and vasoactive products, leukotrienes and chymase, to dengue virus-induced vascular leakage. Elife. 2013 Apr 30;2:e00481.

Published In

Elife

DOI

ISSN

2050-084X

Publication Date

April 30, 2013

Volume

2

Start / End Page

e00481

Location

England

Related Subject Headings

  • Mice
  • Mast Cells
  • Leukotrienes
  • Dengue Virus
  • Chymases
  • Capillary Permeability
  • Animals
  • 42 Health sciences
  • 32 Biomedical and clinical sciences
  • 31 Biological sciences