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1999 Fiscal Year Final Research Report Summary

Platelet Micropartiles, a Carrier of Platelet-Activating Factor, and Remote Organ Failure

Research Project

Project/Area Number 09671228
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionOsaka University

Principal Investigator

KAWASAKI Tomio  MED. SCH. OSAKA UNIV. ASSISTANT PROFESSOR, 医学系研究科, 助手 (90214626)

Co-Investigator(Kenkyū-buntansha) ARIYOSHI Hideo  MED. SCH. OSAKA UNIV. ASSISTANT PROFESSO, 医学系研究科, 助手 (60294055)
SAKON Masato  MED. SCH. OSAKA UNIV. ASSOCIATE PROFESSO, 医学系研究科, 助教授 (40170659)
Project Period (FY) 1997 – 1999
KeywordsPLATELETS / MICROPARTICLES / PLATELET-ACTIVATING FACTOR / REMOTE ORGAN FAILURE / ASPIRIN
Research Abstract

The aim of this study is to evaluate the importance of platelet-microparticles (MPs), a carrier of platelet-activating factor (PAF), in the pathogenesis of remote organ failure in ischemia-reperfusion injury in vascular surgery.
We found that PAF is concentrated and associated with MPs released from high shear stress-induced activated platelets. PAF was released from activated platelets 3 minutes after stimulation. Eighty percent of the PAF released from the platelets was recovered in the MPs fraction, and PAF was 30-fold concentrated in MPs upon stimulation (lwamoto, Kawasaki, BBRC 239, 101-105, 1997). And PAF and 12-HETE but not TXA2 were encapsulated in MPs released from activated platelets.
We investigated the possible existence of MPs in serum LDL fractions. After 10 minutes stimulation of platelet rich plasma with thrombin+collagen, LDL and IDL fractions were obtained. PAF and MPs were identified in LDL and IDL fractions but not in HDL and VLDL fractions. And PAF in MPs is relatively stable and protected from the hydrolysis by acetylhydrolase under physiological condition.
The release of microparticles was identified in severe SIRS, surgical operation and reperfusioninjury after limb salvage. And the patelets were highly potentiated by such insult.
ASA resistance may be caused by an increased sensitivity of platelets to collagen. Platelet aggregation study specific for collagen dose response may be useful for strict selection of ASA responders for lowdose ASA therapy and for identifying ASA non-responders for high-dose ASA therapy (Stroke 31, 591-595, 2000).
These findings are quite important to resolve complications after the insult and to identify the proper medications.

  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Kawasaki T, Ozeki Y., et al.: "increased platelet sensitivity to collagen in individuals resistantto low-dose aspirin"Stroke. 31. 591-595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki T, Shinoki N, et al.: "Diagnostic Value of Plasma Thrombin-Antithrombin III complex and D-Dimer Concentration in Patients with Varicose Veins for Exclusion of Deep-Vein Thrombosis"Thrombos Res. 91. 101-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki T Kambayashi J, et al.: "Hypercholesterolemia as a risk factor for deep-vein thrombosis"Thrombos Res. 88, 1. 67-73 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwamoto S, Kawasaki T., et al.: "The Release Mechanism of Platelet-Activating factor during Shear-Stress Induced Platelet Aggregation"Biochem. Biophys. Res. Commun. 239. 101-105 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okahara K., Kawasaki T., et al.: "Expression of Platelet-activating factor receptor transcript-2 is induced by shear stress in HUVEC"Prostaglandins Other Lipid Mediat. 55. 323-329 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda M., Kawasaki T., et al.: "A role for local calcium gradients upon hypoxic injury in human umbilical vein endothelial cells(HUVEC)"Cell Calcium. 24, 1. 49-57 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki T., Ozeki Y., et al.: "increased platelet sensitivity to collagen in individuals resistantto low-dose aspirin"Stroke. 31. 591-595 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki T., Shinoki N., et al.: "Diagnostic Value of Plasma Thrombin-Antithrombin III complex and D-Dimer Concentration in Patients with Varicose Veins for Exclusion of Deep-Vein Thrombosis"Thrombos Res. 91. 101-104 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki T., Kambayashi J., et al.: "Hypercholesterolemia as a risk factor for deep-vein thrombosis"Thrombos Res. 88, 1. 67-73 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Iwamoto S, Kawasaki T., et al.: "The Release Mechanism of Platelet-Activating factor during Shear-Stress Induced Platelet Aggregation"Biochem. Biophys. Res. Commun. 239. 101-105 (1997)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Okahara K., Kawasaki T., et al.: "Expression of Platelet-activating factor receptor transcript-2 is induced by shear stress in HUVEC"Prostaglandins Other Lipid Mediat. 55. 323-329 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ikeda M., Kawasaki T., et al.: "A role for local calcium gradients upon hypoxic injury in human umbilical vein endothelial cells(HUVEC)"Cell Calcium. 24, 1. 49-57 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川崎富夫: "血小板のダイナミズムとその制御"丸山征郎、池田康夫、尾崎由基男、島田和幸、高井義美編、金芳堂. 12 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩本伸一、川崎富夫: "臨床侵襲学 臨床に生かす侵襲学のすべて"小川道雄、齋藤英昭編、へるす出版. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 川崎富夫: "血小板のダイナミズムとその制御"丸山征郎、池田康夫、尾崎由基男、島田和幸、高井義美編、金芳堂. 12 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩本伸一、川崎富夫: "臨床侵襲学 臨床に生かす侵襲学のすべて"小川道雄、齋藤英昭編、へるす出版. 4 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kawasaki T, Ozeki Y, Igawa T, Kambayashi J.: "Increased platelet sensitivity to collagen in individuals resistant to low-dose aspirin."Stroke. 31. 591-595 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki T, Shinoki N., Iwamoto S., Fujimura H., Yoshikawa N., Ohta Y., Ikeda M., Ariyoshi H., Shibuya T., Monden M.: "Diagnostic Value of Plasma Thrombin-Antithrombin III Complex and D-Dimer Concentration in Patients with Varicose Veins for Exclusion of Deep-Vein Thrombosis."Thrombos Res. 91. 101-104 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kawasaki T, Kambayashi J., Ariyoshi H., Sakon M., Suehisa E, Monden M.: "Hypercholest erolemia as a risk factor for deep-vein thrombosis."Thrombos. Res. 91. 1, 67-73 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Iwamoto S, Kawasaki T., Kambayashi J., Nobutoshi A., Shinoki N., Sakon M., Ikeda Y., Monden M.: "The Release Mechanism of Platelet-Activating factor during Shear-Stress Induced Platelet Aggregation."Biochem. Biophys. Res. Commun.. 239. 101-105 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Okahara K, Sun B, Kawasaki T, Monden M, Kambayashi J.: "Expression of platelet-activating fact or receptor transcript-2 is induced by shear stress in HUVEC."Prostaglandins Other Lipid Mediat. 55. 323-29 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda M, Ariyoshi H., Sakon M., Kambayashi J., Yoshikawa N., Shinoki N., Kawasaki T., Monden M.: "A role for local calcium gradients upon hypoxic injury in human umbilical vein endothelial cells (HUVEC)."Cell Calcium. 24, 1. 49-57 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ikeda M, Kawasaki T., Kambayashi J., Iwamoto S., Shinoki N., Nakamura T., Shibuya T., Monden M.: "Sclerotherapy for Varicose Veins of the Lower Legs in Patients with Dysplasminogenemia."Surgery Todoy.. 27. 714-718 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Miyata T, Kawasaki T., Fujimura H., Uchida K., Tsushima M., Kato H.: "The prothrombin gene G20210A mutation is not found among Japanese patients with deep vein thrombosis and healthy indivisuals."Blood Coagulation and Fibrinolysis. 9 (5). 451-452 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimura H, Kawasaki T., Kambayashi J., Kato H., Monden M., Miyata T.: "Platelet glycoprotein llla P/A Polymorphism and Japanese patients with venous thrombosis."Blood Coagulation and Fibrinolysis. 9. 449-450 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Fujimura H, Kambayashi J., Kato H., Sakon M., Kawasaki T., Ariyoshi H., Suehisa E, Monde M., Miyato T.: "Three Novel Missense Mutations in Unrelated Japanese Patients with Type I and Type II Protein S Deficiency and Venous Thrombosis."Thromb. Res.. 89. 151-160 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura T, Ariyoshi H., Kambayashi J., Ikeda M., Kawasaki T., Sakon M., Monden M.: "Effect of low concentration of epinephrine on human platelet aggregation analyzed by particle counting method and confocal microscopy."J. Lab. Clin. Med.. 30, 3. 262-270 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nakamura T, Ariyoshi H., Kambayashi J., Ikeda M., Shinoki N., Kawasaki T., Monden M.: "Signal transduction system in epinephrine stimulated platelets; comparison between epinephrine sensitive and insensitive platelets."Thromb. Res. 85, 2. 83-93 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Shinoki N, Kawasaki T., Minamino N., Okahara K., Ogawa A., Ariyoshi H., Sakon M., Kambayashi J., Kangawa K., Monden M.: "Shear Stress Down-Regulates Gene Transcription and Production of Adrenomedullin in Human Aortic Endothelial Cells."J of Cellular Biochemistry. 71. 109-115 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshikawa N, Ariyoshi H., Aono Y., Sakon M., Kawasaki T., Monden M.: "Gradients in cytoplasmic calcium concentration ([Ca2+] i) in migrating human umbilical vein endothelial cells (HUVECs) stimulated by shear-stress."Life Science. 65 (24). 2643-2651 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Yoshikawa N, Ariyoshi H, Ikeda M, Sakon M, Kawasaki T, Monden M.: "Shear-stress causes polarized change in cytoplasmic calcium concentration in human umbilical vein endothelial cells (HUVECs)."Cell Calcium.. 22, 3. 189-194 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ariyoshi H, Okahara K., Sakon M., Kambayashi J., Kawashima S., Kawasaki T., Monden M.: "Possible Involvement of m-Calpain in Vascular Smooth Muscle Cell Proliferation."Arterioscler Thromb Vascular Biology. 18. 493-498 (19*)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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