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|Title:||Dengue virus – elicited tryptase induces endothelial permeability and shock||Authors:||Rathore, Abhay P. S.
Mantri, Chinmay Kumar
Aman, Siti A. B.
Jagaraj, Cyril J.
Goh, Chi Ching
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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