IgG-complex stimulated platelets: A source of sCD40L and RANTES in initiation of inflammatory cascade
IgG-complex stimulated platelets: A source of sCD40L and RANTES in initiation of inflammatory cascade
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DOI：
10.1016/j.cellimm.2010.03.009
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发表时间：
2010-01-01
影响因子：
4.3
通讯作者：
Worth, Randall G.
中科院分区：
文献类型：
--
作者：
Antczak, Adam J.;Singh, Navinderjit;Worth, Randall G.
血小板是维持止血的关键因素。血小板的其他功能也得到了重视，如它们在炎症反应和血管重塑中的作用。据报道，血小板与免疫刺激物如IgG复合物结合，并且推测血小板可能参与免疫反应已有近50年的历史。在以前的观察中，我们证明了血小板可以结合和内化聚集的IgG复合物，而不诱导血小板聚集或颗粒释放。为了进一步表征这一观察结果，我们测试了聚集的IgG复合物不激活血小板的假设。为此，用IgG复合物或凝血酶作为阳性对照刺激血小板，并评价其通过聚集、表面标志物表达和细胞因子产生的活化。凝血酶激活导致聚集、高水平的CD 62 P（P-选择素）表达和纤维蛋白原受体α（IIb）β的激活（3）。此外，用凝血酶刺激导致显著量的sCD 40 L（CD 154）和RANTES（CCL 5）。然而，用IgG复合物刺激的血小板导致无聚集和低水平的CD 62 P表达。令人惊讶的是，用聚集的IgG复合物刺激的血小板释放与凝血酶活化的血小板相似量的sCD 40 L和RANTES。这些数据表明，血小板能够响应IgG复合物分泌炎性分子。(C)2010年爱思唯尔公司All rights reserved.
Platelets are a crucial element in maintenance of hemostasis. Other functions attributable to platelets are now being appreciated such as their role in inflammatory reactions and vascular remodeling. Platelets have been reported to bind immunological stimuli like IgG-complexes and the understanding that platelets may participate in immunological reactions has been speculated for nearly 50 years. In previous observations, we demonstrated that platelets could bind and internalize aggregated IgG-complexes without inducing platelet aggregation or granule release. To characterize this observation further, we tested the hypothesis that aggregated IgG-complexes do not activate platelets. To this end, platelets were stimulated with IgG-complexes or thrombin as a positive control and evaluated for activation by aggregation, expression of surface markers and production of cytokines. Activation with thrombin resulted in aggregation, expression of high levels of CD62P (P-selectin) expression and activation of the fibrinogen receptor, alpha(IIb)beta(3). Furthermore, stimulation with thrombin resulted in significant amounts of sCD40L (CD154) and RANTES (CCL5). However, platelets stimulated with IgG-complexes resulted in no aggregation and low levels of CD62P expression. Surprisingly, platelets stimulated with aggregated IgG-complexes released similar amounts of sCD40L and RANTES as platelets activated by thrombin. These data suggest that platelets are capable of secreting inflammatory molecules in response to IgG-complexes. (C) 2010 Elsevier Inc. All rights reserved.