| Project/Area Number |
18591096
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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 |
膠原病・アレルギー・感染症内科学
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| Research Institution | Hokkaido University |
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Principal Investigator |
TATSUYA Atsumi Hokkaido University, Hokkaido University Hospital, Lecturer (20301905)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | antiphospholipid antibody / thrombosis / phosphatidylserine / prothrombin / beta-glycoprotein I / lipid scramblase / tissue factor / p38MAPK / β2-グリコプロテイン |
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| Research Abstract |
1. It is worldwide accepted that the interaction between 82glycopmtein I-dependent anticardiolipin antibodies (aCL/β2GPI) and β2GPI triggers tissue factor (TF) expression, leading to thrombotic events in patients with antiphospholipid syndrome. In this study we evaluated the link of lipid scramblase 1(LSCR1) and TF induction mediated by monoclonal aCL/β2GPI in a murine monocyte cell line. Three hours pre-treatment with INFa increased the LSCR1mRNA levels when incubated with aCL/β2GPI Pre-treatment with INFa enhanced TF mRNA induction by aCL/β2GPI (3.8 fold average rise of ratio. INFa enhanced the effect of aCL/β2GPI on TF mRNA expression. The effect of INFa presumably leads to PS expression on cell surface and might facilitate the accessibility of PL- binding proteins, followed by further aPL interaction
2. We have shown that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) are as prevalent as aCL/b2GPI in patients with APS, and represent a possible marker of APS. In this study, we explored the activated intracellular signals in monocytes treated with monoclonal aPS/PT and correlated with TF expression. 231D was established and characterized as murine monoclonal aPS/PT. Upregulated TF mRNA expression was detected only in the presence of prothrombin and CaCl2 on PBMC and RAW264.7 treated with 231D. The array showed increased phosphorylation of p38 MAPK on PBMC treated with 231D in the presence of prothrombin compared with its absence. The phosphorylation of neither JNK nor ERK1/2 was evident on 231D-treated PBMC. The elevated phosphorylation of p38-MAPK was confirmed by the cell ELISA on RAW264.7 treated with a combination of prothrombin and 231D.. ACL/b2GPI and aPS/PT may share the activating pathway to induce TF on monocytes and the phenomena may correlate to the thrombogenicity of aPL with lupus anticoagulant activity.
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