Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases.
Dengue induces platelet activation, mitochondrial dysfunction and cell death through mechanisms that involve DC-SIGN and caspases.
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DOI：
10.1111/jth.12178
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Bozza FA
中科院分区：
文献类型：
--
作者：
Hottz ED;Oliveira MF;Nunes PC;Nogueira RM;Valls-de-Souza R;Da Poian AT;Weyrich AS;Zimmerman GA;Bozza PT;Bozza FA
登革热是世界上最流行的人类虫媒病毒病。登革热感染可引起一系列临床表现，从自限性发热性疾病到伴有出血和休克的危及生命的综合征。血小板减少症在轻度和重度疾病中经常观察到，然而，DENV诱导的血小板活化和血小板减少症的机制尚不完全清楚。对登革热患者新鲜分离的血小板进行了活化标记物、线粒体改变和细胞死亡途径活化的评价。同时，我们确定DENV是否诱导从健康受试者获得的血小板的直接活化和凋亡。我们发现，与对照受试者相比，DENV感染患者的血小板显示出增加的活化。此外，来自DENV感染患者的血小板表现出细胞凋亡内在途径的经典迹象，包括增加的表面磷脂酰丝氨酸暴露、线粒体去极化和caspase-9和3的活化。事实上，在DENV感染患者中，血小板减少症与血小板活化增强和细胞死亡密切相关。当来自健康受试者的血小板在体外直接暴露于DENV时，还观察到血小板活化、线粒体功能障碍和血小板上的半胱天冬酶依赖性磷脂酰丝氨酸暴露。DENV诱导的血小板活化显示通过在很大程度上依赖于DC-SIGN的机制发生。总之，我们的研究结果表明，从登革热患者的血小板目前的迹象，激活，线粒体功能障碍，和激活的凋亡caspase级联反应，这可能有助于在登革热患者血小板减少症的发生。我们的研究结果还表明，DC-SIGN作为一个关键的受体参与DENV依赖性血小板活化。
Dengue is the most prevalent human arbovirus disease in the world. Dengue infection may cause a range of clinical manifestation from self-limiting febrile illness through life-threatening syndrome accompanied by bleeding and shock. Thrombocytopenia is frequently observed in mild and severe disease, however the mechanisms involved in DENV-induced platelet activation and thrombocytopenia are incompletely understood. Freshly-isolated platelets from patients with dengue were evaluated for markers of activation, mitochondrial alterations and activation of cell death pathways. In parallel, we determined whether DENV induced direct activation and apoptosis of platelets that were obtained from healthy subjects. We found that platelets from DENV-infected patients display increased activation when compared to control subjects. Moreover, platelets from DENV-infected patients exhibited classic signs of the intrinsic pathway of apoptosis that include increased surface phosphatidylserine exposure, mitochondrial depolarization and activation of caspase-9 and 3. Indeed, thrombocytopenia was shown to strongly associate with enhanced platelet activation and cell death in DENV-infected patients. Platelet activation, mitochondrial dysfunction and caspase-dependent phosphatidylserine exposure on platelets were also observed when platelets from healthy subjects were directly exposed to DENV in vitro. DENV-induced platelet activation was shown to occur through mechanisms largely dependent of DC-SIGN. Together our results demonstrate that platelets from patients with dengue present signs of activation, mitochondrial dysfunction, and activation of apoptosis caspase cascade, which may contribute to the genesis of thrombocytopenia in patients with dengue. Our results also suggest the involvement of DC-SIGN as a critical receptor in DENV-dependent platelet activation.
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影响因子：
3.7
作者：
Alves LR;Costa ES;Sorgine MH;Nascimento-Silva MC;Teodosio C;Bárcena P;Castro-Faria-Neto HC;Bozza PT;Orfao A;Oliveira PL;Maya-Monteiro CM
通讯作者：
Maya-Monteiro CM
影响因子：
64.5
作者：
Mason, Kylie D.;Carpinelli, Marina R.;Kile, Benjamin T.
通讯作者：
Kile, Benjamin T.
影响因子：
3.6
作者：
Fitzgerald, JR;Loughman, A;Foster, TJ
通讯作者：
Foster, TJ
影响因子：
10.4
作者：
Leytin, V.;Allen, D. J.;Freedman, J.
通讯作者：
Freedman, J.
DOI：
10.4269/ajtmh.2009.80.841
发表时间：
2009-05-01
影响因子：
3.3
作者：
Honda, Shoko;Saito, Mariko;Oishi, Kazunori
通讯作者：
Oishi, Kazunori