Imaging analysis of phosphatidylserine-evoked initiation of coagulation cascade on activated platelets surface.
| Project/Area Number |
21590230
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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 |
General physiology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Yuko 浜松医科大学, 医学部, 准教授 (20345812)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2009: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
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| Keywords | 血液凝固 / 血液レオロジー / 線溶 |
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| Research Abstract |
(1) Analyses of the regulatory mechanisms on PS exposure on platelets' surface and its contribution to micro-particle bearing TF-evoked activation of coagulation cascade.
Exposure of PS on platelets' surface plays essential role in thrombus formation. Based on our recent finding in in-vivo study that platelets expose PS only when they exist in the center of the thrombus, we analyzed the factors to regulate PS exposure on platelets surface. To elucidate how PS exposure is regulated within the thrombus, we analyzed PS exposure on platelets existing in fibrin network using diluted platelet-rich plasma by Confocal Laser Scanning Microscopy. Almost all platelets bound to fibrin scaffold and exposed PS after treatment with TF, thrombin or ionomycin. An attenuation of fibrin mesh formation by several pharmacological methods suppressed PS exposure. FK633, a GPIIb/IIIa antagonist, entirely inhibited fibrin(ogen) binding abrogated fibrin network formation, but also reduced PS exposure without suppressing fibrin(ogen) binding. Cytochalasin B impaired both platelets' binding to fibrin(ogen) and PS exposure. These results suggest that GPIIb/IIIa-mediated outside-in signals in platelets generated by the binding to fibrin scaffold and the associated mechanical foci, appear to be essential for PS exposure. Such regulation of platelet PS exposure may play an important role in the control of hemostasis.(submitted)
U937 cells were treated by calcium ionophore, and TF bearing microparticles were obtained. Supplementation of the TF-bearing microparticle to the system mentioned above, successfully generated fibrin network. We stared to analyze the space-and time-dependent interaction between TF bared on microparticle and PS exposed on activated platelets both of which are essential to activate coagulation cascade.
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Report
(4 results)
Research Products
(71 results)
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[Journal Article] In vivo imaging visualizes discoid platelet aggregations without endothelium disruption and implicates contribution of inflammatory cytokine and integrin signaling2012
Author(s)
Nishimura S, Manabe I, Nagasaki M, Kakuta S, Iwakura Y, TakayamaN, Ooehara J, Otsu M, Kamiya A, Petrich B, Urano T, Kadono T, Sato S, Aiba A, Yamashita H, Sugiura S, Kadowaki T, Nakauchi H, Eto K, and Nagai R
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Journal Title
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[Journal Article] Life-threatening haemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete PAI-1 deficiency in humans2011
Author(s)
Iwaki T, Tanaka A, Miyawaki Y, Suzuki A, Kobayashi T, Takamatsu J, Matsushita T, Umemura K, Urano T, Kojima T, Terao T, Kanayama N
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Journal Title
Journal of Thrombosis and Haemostasis
Volume: 9(6)
Pages: 1200-1206
Related Report
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[Journal Article] A novel phospha sugar analogue : synthesis and evaluation of 2, 3-dibromo-3-methyl-1-phenylphospholane 1-oxide as a new class of potential panti-proliterative materials for leukemia cells2009
Author(s)
Fujie M, Nakamura S, Asai K, Niimi T, Yamashita J, Kiyofuji K, Shibata K, Suzuki M, Aoshima R, Urano T and Yamashita M
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Journal Title
Heterocyclic Communications
Volume: 15(4)
Pages: 273-278
Related Report
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[Journal Article] A technique for monitoring multiple signals with a combination of prism-based total internal reflection fluorescence microscopy and epifluorescence microscopy2009
Author(s)
Adachi E, Kazoe Y, Sato Y, Suzuki Y, Urano T, Ueyama T, Saito N, Nikolaev VO, Lohse MJ, Tominaga M, Mogami H
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Journal Title
Pflugers Arch-Eur J Physiol
Volume: 459(1)
Pages: 227-34
Related Report
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[Journal Article] E A technique for monitoring multiple signals with a combination of prism-based total internal reflection fluorescence microscopy and epifluorescence microscopy2009
Author(s)
Adachi E, Kazoe Y, Sato Y, Suzuki Y, Urano T, Ueyama T, Saito N, Nikolaev VO, Lohse MJ, Tominaga M, Mogami H.
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Journal Title
Pflugers Arch-Eur J Physiol 459(1)
Pages: 227-34
Related Report
Peer Reviewed
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[Journal Article] Life-threatening haemorrhage and prolonged wound healing are remarkable phenotypes manifested by complete PAI-1 deficiency in humans.
Author(s)
Iwaki T, Tanaka A, Miyawaki Y, Suzuki A, Kobayashi T, Takamatsu J, Matsushita T, Umemura K, Urano T, Kojima T, Terao T, Kanayama N.
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Journal Title
Journal of Thrombosis and Haemostasis
Volume: (In press)
Related Report
Peer Reviewed
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[Journal Article] A novel phospha sugar analogue : synthesis and evaluation of 2,3-dibromo-3-methyl-1-phenylphospholane 1-oxide as a new class of potential panti-proliterative materials for leukemia cells
Author(s)
Fujie M, Nakamura S, Asai K, Niimi T, Yamashita J, Kiyofuji K, Shibata K, Suzuki M, Aoshima R, Urano T, Yamashita M
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Journal Title
Heterocyclic Communications (In press)
Related Report
Peer Reviewed
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