Details

Autor(en) / Beteiligte

• Chu, Ya-Ting
• Wan, Shu-Wen
• Chang, Yu-Chang
• Lee, Chien-Kuo
• Wu-Hsieh, Betty A
• Anderson, Robert
• Lin, Yee-Shin

Titel

Antibodies against nonstructural protein 1 protect mice from dengue virus-induced mast cell activation

Ist Teil von

• Laboratory investigation, 2017-05, Vol.97 (5), p.602-614

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

Elektronische Zeitschriftenbibliothek (Open access)

Beschreibungen/Notizen

• Dengue virus (DENV) infection causes dengue fever, dengue hemorrhagic fever (DHF), and dengue shock syndrome (DSS). DHF/DSS patients have been reported to have increased levels of urinary histamine, chymase, and tryptase, which are major granule-associated mediators from mast cells. Previous studies also showed that DENV-infected human mast cells induce production of proinflammatory cytokines and chemokines, suggesting a role played by mast cells in vascular perturbation as well as leukocyte recruitment. In this study, we show that DENV but not UV-inactivated DENV enhanced degranulation of mast cells and production of chemokines (MCP-1, RANTES, and IP-10) in a mouse model. We have previously shown that antibodies (Abs) against a modified DENV nonstructural protein 1 (NS1), designated DJ NS1, provide protection in mice against DENV challenge. In the present study, we investigate the effects of DJ NS1 Abs on mast cell-associated activities. We showed that administration of anti-DJ NS1 Abs into mice resulted in a reduction of mast cell degranulation and macrophage infiltration at local skin DENV infection sites. The production of DENV-induced chemokines (MCP-1, RANTES, and IP-10) and the percentages of tryptase-positive activated mast cells were also reduced by treatment with anti-DJ NS1 Abs. These results indicate that Abs against NS1 protein provide multiple therapeutic benefits, some of which involve modulating DENV-induced mast cell activation.