| Project/Area Number |
13557213
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
医薬分子機能学
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| Research Institution | Hoshi University |
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Principal Investigator |
TSUJI Tsutomu Hoshi University, Professor, 薬学部, 教授 (00143503)
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| Co-Investigator(Kenkyū-buntansha) |
MASUDA Junichi Shimane University, Professor, 医学部, 教授 (70173747)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2001: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | P-selectin / Cell adhesion / Platelet / Leukocyte / Reactive oxygen species / Sialic acid / Sulfated carbohydrate / Hemodialysis / 抗接着療法 / 活性酸素 / 生体適合性 / 炎症反応 / 腫瘍壊死因子 / 細胞表面糖鎖 |
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| Research Abstract |
P-selectin mediates cell adhesion between platelets/endothelial cells and leukocytes, and plays a crucial role in the recruitment of leukocytes into hemorrhagic and inflammatory sites. Furthermore, the interaction causes the functional activation of leukocytes including reactive oxygen species (ROS) and cytokine production by leukocytes. In this study, 1) we attempted to regulate the interaction by a carbohydrate-based inhibitor, and 2) we characterized the leukocyte activation caused by the platelet-leukocyte interaction during hemodialysis.
1.Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of sialic acid : We examined effects of a synthetic sulfated derivative of sialic acid (NMSO3) on P-selectin-mediated cell adhesion and found the following. 1) The binding of P-selectin/IgG chimera to purified P-selectin glycoprotein ligand-1 was inhibited by soluble NMSO3. 2) The adhesion of HL6O cells to P-selectin-expressing CHO cells was inhibited by NMSO3. 3) NMSO3 inhibited P-selectin-induced tumor necrosis factor-α production in monocytes and activated platelet-induced generation of reactive oxygen species in neutrophils. In conclusion, NMSO3 acts as a specific inhibitor for P-selectin-mediated cell adhesion and for adhesion-dependent leukocyte activation.
2.Leukocyte activation through the adhesion with activated platelets during hemodialysis : Platelets were more easily activated by the contact with dialyzer membranes composed of hydrophobic materials than by that of hydrophilic materials. The activated platelets then adhered to leukocytes and induced ROS production by leukocytes. Therefore, the interaction between platelets and hemodialysis membranes is one of the key factors to determine their biocompatibility.
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