Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/142486
Title: Dengue virus – elicited tryptase induces endothelial permeability and shock
Authors: Rathore, Abhay P. S.
Mantri, Chinmay Kumar
Aman, Siti A. B.
Syenina, Ayesa
Ooi, Justin
Jagaraj, Cyril J.
Goh, Chi Ching
Tissera, Hasitha
Wilder-Smith, Annelies
Ng, Lai Guan
Gubler, Duane J.
St. John, Ashley L.
Keywords: Science::Biological sciences
Issue Date: 2019
Source: Rathore, A. P. S., Mantri, C. K., Aman, S. A. B., Syenina, A., Ooi, J., Jagaraj, C. J., . . . St. John, A. L. (2019). Dengue virus – elicited tryptase induces endothelial permeability and shock. The Journal of Clinical Investigation, 129(10), 4180-4193. doi:10.1172/JCI128426
Journal: The Journal of Clinical Investigation
Abstract: Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we showed that an MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in 2 independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock.
URI: https://hdl.handle.net/10356/142486
ISSN: 0021-9738
DOI: 10.1172/JCI128426
Rights: © 2019 American Society for Clinical Investigation. This is an open-access article distributed under the terms of the Creative Commons Attribution License.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SBS Journal Articles

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