Mechanism of platelet activation by Helicobacter Pylori

特发性血小板减少性紫癜(ITP)是一种以自身抗体介导的血小板破坏为特征的疾病，可能是各种疾病的原发病或继发性疾病，包括淋巴增生性自身免疫或感染性疾病。有关幽门螺杆菌感染与特发性血小板减少性紫癜的相关性以及根除细菌后血小板计数的显著增加的数据越来越多。这些结果表明，幽门螺杆菌感染可诱导血栓形成过程中的血小板活化。本研究旨在探讨幽门螺杆菌空泡毒素VacA诱导血小板活化的机制。血小板与内皮下结构的黏附是止血和血栓形成的早期和关键事件。血管性血友病因子(VWF)是一种主要的粘附性糖蛋白(GP)，在高切应力条件下(如小动脉和动脉毛细血管)需要正常止血。在…面前更多的高切应力或调节剂，如Botrocetin，VWF，结合到血小板膜GPIB-IX-V复合体上，启动细胞内信号，导致血小板激活。在本研究中，我们发现VacA以浓度依赖的方式诱导血小板释放P选择素。120 nm VacA诱导血小板释放最大P选择素。VacA还可诱导VWF与GPIB结合所刺激的血小板聚集性增加。最近人们认识到细胞膜是不均匀的，并且存在特定的膜区，富含胆固醇和糖磷脂，称为糖鞘糖脂富集型微域(GEMS，也称为RAFT)。GEMS包含特定的信号分子，同时排除其他分子，似乎为信号转导提供了平台。生物素标记的VacA研究表明，VacA与一种未知的血小板受体结合，该受体位于宝石中。CNBR-VacA分析表明，130 kDa的血小板膜糖蛋白与血小板膜上的VacA有关。这些结果提示，幽门螺杆菌可引起VWF-GPIB相关途径的血小板活化，从而导致血栓的形成，而VacA诱导的血小板活化机制可预防血栓性疾病。较少

Idiopatic thrombocytopenic purpura (ITP), a disorder characterized by autoantibody-mediated platelet destruction, may be primary or seconday to various illness including lymphoproliferative autoimmune, or infectious diseases. There are increasing data on the association between Helicobacter pylori infection and idipatic thrombocytopenic purupura and the significant increase of in platelet count after bacterial eradication. These results suggest that Helicobacter pyroli infection induces platelet activation in thrombus formation. The aim of this study is to consider the mechanism of platelet activation induced by VacA, Helicobacter pylori vacuolating cytotoxin. Platelet adhesion to subendothelial structure is an early and critical event in hemostasis and thrombosis. von Willebrand factor (VWF) is a major adhesive glycoprotein (GP) required for normal hemostasis under condition of high shear stress, such as those that occur in small arterioles and arterial capillaries. In the presence of … More high shear stress or modulators such as botrocetin, VWF binds to the platelet membrane GPIb-IX-V complex and initiates intracellular signals leading to platelet activation. In this study, we found that VacA induces increase of release of P selectin from platelet in a concentration-dependent manner. 120nM VacA induces maximum of release of P selection from platelets. VacA also induced increase of platelet aggregation stimulated by VWF binding to GPIb. It has been recently recognized that cell membranes are not uniform and that there are particular membrane regions rich in cholesterol and glycosphinglipids known as glycosphingolipid-enriched microdomains (GEMs, also known as raft). GEMs contain certain sets of signaling molecules whilst excluding others, and appear to provide platforms for signal transduction. Biotin-labelled VacA study revealed that VacA associates an unknown platelet receptor, which locates in GEMs. The analysis by CNBr-VacA showed that 130kDa of platelet glycoprotein is associated with VacA in platelet membranes. These results suggest that Helicobacter pylori cause platelet activation in VWF-GPIb-related pathways, leading to thrombus formation, and that mechanism of platelet activation induced by VacA would prevent thrombotic disorders. Less