CD40 ligand influences platelet release of reactive oxygen intermediates
CD40 ligand influences platelet release of reactive oxygen intermediates
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DOI：
10.1161/01.atv.0000184765.59207.f3
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发表时间：
2005-11-01
影响因子：
8.7
通讯作者：
Freedman, JE
中科院分区：
文献类型：
--
作者：
Chakrabarti, S;Varghese, S;Freedman, JE
目的可溶性CD40配体(SCD40L)参与动脉粥样硬化的发病机制。急性冠脉综合征患者sCD40L水平升高提示血小板功能增强；然而，其确切发生机制尚不清楚。在这项研究中，我们检测了sCD40L对血小板功能和活性氧氮物种(RONS)生成的影响。方法和结果-通过DCFHDA氧化和共聚焦显微镜检测，重组sCD40L(RsCD40L)对血小板刺激导致RONS生成增加。与rsCD40L孵育后，血小板P-选择素表达增强，聚集性增强，血小板-白细胞结合增强。与野生型小鼠相比，CD40L缺陷小鼠分离的血小板减少了激动剂诱导的NO释放。结论可溶性CD40L可促进刺激诱导的血小板活化、聚集和血小板-白细胞结合，并通过激活Akt和p38 MAP激酶信号通路增加刺激诱导的血小板释放rons。这些数据表明，sCD40L调节血小板依赖性炎症和血栓反应，这些反应参与了动脉粥样硬化血栓形成的发病机制。
Objective-Soluble CD40 ligand (sCD40L) has been recently implicated in the pathogenesis of atherosclerosis. Elevated levels of sCD40L in acute coronary syndrome patients suggests enhanced platelet function; however, the exact mechanism by which this occurs is unknown. In this study, we examined the effect of sCD40L on platelet function and reactive oxygen and nitrogen species (RONS) generation.Methods and Results-Platelet stimulation in the presence of recombinant sCD40L (rsCD40L) led to enhanced generation of RONS as measured by DCFHDA oxidation and confocal microscopy. Incubation with rsCD40L led to enhanced platelet P-selectin expression, aggregation, and platelet-leukocyte conjugation. Platelets isolated from CD40L-deficient mice had decreased agonist-induced NO release as compared with wild-type mice. Incubation of platelets with rsCD40L enhanced stimulation-induced p38 MAP kinase and Akt phosphorylation.Conclusion-Soluble CD40L enhances platelet activation, aggregation, and platelet-leukocyte conjugation, as well as increases stimulation-induced platelet release of RONS through activation of Akt and p38 MAP kinase signaling pathways. These data suggest that sCD40L regulates platelet-dependent inflammatory and thrombotic responses that contribute to the pathogenesis of atherothrombosis.