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，可能是多种疾病的原发或继发，包括淋巴增生性自身免疫性疾病或感染性疾病。越来越多的数据表明幽门螺杆菌感染与特发性血小板减少性紫癜之间存在关联，并且清除细菌后血小板计数显著增加。这些结果提示，在血栓形成过程中，幽门螺杆菌感染可诱导血小板活化。本研究旨在探讨幽门螺杆菌空泡细胞毒素VacA诱导血小板活化的机制。血小板粘附到内皮下结构是止血和血栓形成的早期和关键事件。血管性血液病因子（VWF）是一种主要的黏附糖蛋白（GP），在高剪切应力条件下，如小动脉和动脉毛细血管中发生的剪切应力，需要正常止血。当存在更高的剪切应力或botrocetin等调节剂时，VWF与血小板膜GPIb-IX-V复合物结合并启动细胞内信号导致血小板活化。在本研究中，我们发现VacA诱导血小板P选择素的释放以浓度依赖性的方式增加。120nM VacA诱导血小板最大限度地释放P选择。VWF与GPIb结合后，VacA还能诱导血小板聚集增加。最近已经认识到细胞膜不是均匀的，并且存在富含胆固醇和鞘脂糖的特定膜区域，称为鞘脂糖富集微域（GEMs，也称为筏）。GEMs包含某些信号分子，同时排除其他信号分子，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相关，该受体位于gem中。CNBr-VacA分析显示血小板糖蛋白130kDa与血小板膜上的VacA相关。这些结果提示幽门螺杆菌通过vwf - gpib相关通路激活血小板，导致血栓形成，而VacA诱导血小板激活的机制可以预防血栓性疾病。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