| Project/Area Number |
16590449
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Laboratory medicine
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| Research Institution | University of Yamanashi |
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Principal Investigator |
ASAZUMA Naoki University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Assistant Professor, 大学院・医学工学総合研究部, 講師 (60293445)
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| Co-Investigator(Kenkyū-buntansha) |
OZAKI Yukio University of Yamanashi, Department of Research Interdisciplinary Graduate School of Medicine and Engineering, Professor, 大学院・医学工学総合研究部, 教授 (30134539)
SATOH Kaneo University of Yamanashi, Faculty of Medicine, Educational Official, 医学部, 教務職員 (20242662)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2005: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2004: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | platelets / Helicobacter Pylori / VacA / GPIb / von Willebrand factor / GEMs / platelet aggregation / platelet activation / ヘリコバクター・ピロリ / VWF |
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| Research Abstract |
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
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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
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