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IgG 包被的靶标的内化导致人血小板激活并分泌可溶性 CD40 配体和趋化因子RANTES。

Internalization of IgG-coated targets results in activation and secretion of soluble CD40 ligand and RANTES by human platelets.

作者信息

Antczak Adam J, Vieth Joshua A, Singh Navinderjit, Worth Randall G

机构信息

Department of Medical Microbiology and Immunology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.

出版信息

Clin Vaccine Immunol. 2011 Feb;18(2):210-6. doi: 10.1128/CVI.00296-10. Epub 2010 Dec 22.

DOI:10.1128/CVI.00296-10
PMID:21177916
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3067351/
Abstract

Platelets are crucial elements for maintenance of hemostasis. Other functions attributable to platelets are now being appreciated, such as their role in inflammatory reactions and host defense. Platelets have been reported to bind immunological stimuli like IgG complexes, and for nearly 50 years it has been speculated that platelets may participate in immunological reactions. Platelets have been reported to bind and internalize various substances, similar to other leukocytes, such as macrophages and dendritic cells. In the present study, we tested the hypothesis that human platelets can bind and internalize IgG-coated particles, similar to leukocytes. To this end, we observed that interaction with IgG-coated beads resulted in platelet activation (as measured by CD62P expression), internalization of targets, and significant soluble CD40 ligand (sCD40L) and RANTES (regulated upon activation, normal T cell expresses and secreted) secretion. Blocking FcγRIIA with monoclonal antibody (MAb) IV.3 or inhibiting actin remodeling with cytochalasin D inhibited platelet activation, internalization, and cytokine production. These data suggest that platelets are capable of mediating internalization of IgG-coated particles, resulting in platelet activation and release of both sCD40L and RANTES.

摘要

血小板是维持止血的关键要素。现在人们也认识到血小板的其他功能,比如它们在炎症反应和宿主防御中的作用。据报道,血小板能结合免疫刺激物,如IgG复合物,近50年来一直有人推测血小板可能参与免疫反应。据报道,血小板能像其他白细胞(如巨噬细胞和树突状细胞)一样结合并内化各种物质。在本研究中,我们检验了一个假设,即人类血小板能像白细胞一样结合并内化IgG包被的颗粒。为此,我们观察到与IgG包被的珠子相互作用会导致血小板活化(通过CD62P表达来衡量)、靶标的内化以及可溶性CD40配体(sCD40L)和RANTES(活化时表达和分泌,正常T细胞表达和分泌)的大量分泌。用单克隆抗体(MAb)IV.3阻断FcγRIIA或用细胞松弛素D抑制肌动蛋白重塑可抑制血小板活化、内化和细胞因子产生。这些数据表明血小板能够介导IgG包被颗粒的内化,从而导致血小板活化以及sCD40L和RANTES的释放。

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本文引用的文献

1
IgG-complex stimulated platelets: a source of sCD40L and RANTES in initiation of inflammatory cascade.免疫球蛋白 G 复合物刺激的血小板:炎症级联反应中 sCD40L 和 RANTES 的来源。
Cell Immunol. 2010;263(1):129-33. doi: 10.1016/j.cellimm.2010.03.009. Epub 2010 Mar 20.
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Platelet functions beyond hemostasis.血小板的止血功能以外的作用。
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Toll-like receptor 4 ligand can differentially modulate the release of cytokines by human platelets.Toll样受体4配体可不同程度地调节人血小板细胞因子的释放。
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Moderation of the platelet releasate response by aspirin.阿司匹林对血小板释放物反应的调节作用。
Blood. 2007 Jun 1;109(11):4786-92. doi: 10.1182/blood-2006-07-038539. Epub 2007 Feb 15.
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Platelet FcgammaRIIA binds and internalizes IgG-containing complexes.血小板FcγRIIA结合并内化含IgG的复合物。
Exp Hematol. 2006 Nov;34(11):1490-5. doi: 10.1016/j.exphem.2006.06.015.
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