血小板はどこでどのように産生されるか

2015 Fiscal Year Annual Research Report

• Project/Area Number: 25461458
• Research Institution: Iwate Medical University
• Principal Investigator: 石田 陽治 岩手医科大学, 医学部, 教授 (70151389)
• Co-Investigator(Kenkyū-buntansha): 古和田 周吾 岩手医科大学, 医学部, 講師 (30418884) ; 伊藤 薫樹 岩手医科大学, 医学部, 教授 (60316362)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 血小板産生 / proplatelet / preplatelet / thick protrusion

Outline of Annual Research Achievements

今年度の目的は、(1) 血小板前駆体がどのように末梢血中で成熟血小板に変化するものかを、また、(2) 血管床のどこで変化するかを明らかにすることであった。
(1) 血小板前駆体がどのように成熟血小板に変化するか？
何も刺激しないGFPマウスの静脈血を腹部大静脈から採取し、スメアを作成した。その中で、胞体突起やthick protrusionをしめす血小板前駆体は数％しか認められなかった。そこで、その比率を増やすために、GFPマウスに抗血小板抗体を投与し、経時的にその比率を調べたところ、抗血小板抗体投与後４８時間後にその比率は１０数％に増加した。以後の実験は抗血小板抗体投与後４８時間時のマウス静脈血を用いて行った。５時間のin vitro培養で、thick protrusionは数珠状の形態に変化し、成熟血小板よりも数倍大きな腫瘤へと切断されて行ったが、その切断にはさらに数時間要した。が全て切断されたわけではなかった。切断された腫瘤状のものはさらに培養を続けていくと細長いproplateletように伸びていき、そこには、成熟血小板と同じ大きさの程度の腫瘤状のものに変化して行った。切断にはさらに数時間要したが、全て切断されたわけではなかった。これらから、切断には、血流などのズリ応力が必要かもしれないと思われた。
(2) 血管床のどこで変化するか?
マウスにGFP陽性血小板前駆体を投与後、経時的に肺の血管床を採取し、固定した。GFP陽性血小板前駆体を肺の血管床で認めた。２光子顕微鏡で撮影しようと試みたが、肺の呼吸に伴って血管床が上下に動くため、イメージをキャプチャーすることは無理であった。
以上より、血小板前駆体は、次第に成熟血小板に変化していくものと思われた。

Research Products

• [Journal Article] Pharmacokinetics and pharmacodynamics of dasatinib in the chronic phase of newly diagnosed chronic myeloid leukemia (2016)
  • Author(s): Ishida Y, Murai K, Yamaguchi K, Miyagishima T, Shindo M, Ogawa K, Nagashima T, Sato S, Watanabe R, Yamamoto S, Hirose T, Saitou S, Yonezumi M, Kondo T, Kato Y, Mochizuki N, Ohno K, Kishino S, Kubo K, OyakeT, Ito S, Inter-Michinoku Dasatinib Study Group
  • Journal Title: Eur J Clin Pharmacol Volume: 72 Pages: 185-193
  • DOI: 10.1007/s00228-015-1968-y
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Comparison of micafungin and voriconazole as empirical antifungal therapies in febrile neutropenic patients with hematological disorders: a randomized controlled trial (2016)
  • Author(s): Oyake, T. Kowata, S. Murai, K. Ito, S. Akagi, T. Kubo, K. Sawada, K. Ishida, Y.
  • Journal Title: Eur J Haematol Volume: 96 Pages: 602-609
  • DOI: 10.1111/ejh.12641
  • Peer Reviewed
• [Journal Article] A prospective analysis of clinical efficacy and safety in chronic myeloid leukemia-chronic phase patients with imatinib resistance or intolerance as evaluated using European LeukemiaNet 2013 criteria (2015)
  • Author(s): Kazunori Murai, Tomoaki Akagi, Kenji Shimosegawa, Tomohiro Sugawara, Kenichi Ishizawa, Shigeki Ito, Keiko Murai, Mutsuhito Motegi, Hisayuki Yokoyama, Hideyoshi Noji, Katsushi Tajima, Jun Kimura, Takaaki Chou, Kazuei Ogawa, Hideo Harigae, Kohmei Kubo, Koji Oba, Junichi Sakamot, Yoji Ishida
  • Journal Title: European Journal of Haematology Volume: 95 Pages: 558-565
  • DOI: 10.1111/ejh.12536
  • Peer Reviewed
• [Journal Article] YM155 suppresses cell proliferation and induces cell death in human adult T-cell leukemia/lymphoma cells (2015)
  • Author(s): Sasaki R, Ito S, Asahi M, Ishida Y
  • Journal Title: Leuk Res Volume: 39 Pages: 1473-1479
  • DOI: 10.1016/j.leukres.2015.10.012
  • Peer Reviewed
• [Journal Article] Discontinuation of dasatinib in patients with chronic myeloid leukaemia who have maintained deep molecular response for longer than 1 year (DADI trial): a multicentre phase 2 trial (2015)
  • Author(s): Imagawa, J. Tanaka, H. Okada, M. Nakamae, H. Hino, M. Murai, K. Ishida, Y. Kumagai, T. Sato, S. Ohashi, K. Sakamaki, H. Wakita, H. Uoshima, N. Nakagawa, Y. Minami, Y. Ogasawara, M. Takeoka, T. Akasaka, H. Utsumi, T. Uike, N. Sato, T. Ando, S. Usuki, K. Morita, S. Sakamoto, J. Kimura, S. Dadi Trial Group
  • Journal Title: Lancet Haematol Volume: 2 Pages: e528-35
  • DOI: 10.1016/S2352-3026(15)00196-9
  • Peer Reviewed
• [Presentation] Velocity of Early BCR-ABL Transcript Elimination As an Optimized Predictor of Deep Molecular Response in Chronic Myeloid Leukemia Patients in Chronic Phase on Treatment with Dasatinib (2015)
  • Author(s): Kazunori Murai, Kohei Yamaguchi, Shigeki Ito, Tomoaki Akagi, Kazuei Ogawa, Inomata Mitsue, Kuniaki Meguro, Reiko Watanabe, Takuto Miyagishima, Kentaro Wakasa, Motohiro Shindo, Yasuhiko Tsukushi, Kohmei Kubo, Koji Oba, Junichi Sakamoto and Yoji Ishida,
  • Organizer: 57th Annual Meeting of America Society of Hematology
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2015-12-07
  • Int'l Joint Research
• [Presentation] Recombinant Thrombomodulin for the Treatment of Transplantation-Associated Coagulopathy after Allogeneic Hematopoietic Stem Cell Transplantation: A Multi-Center Study in Japan (2015)
  • Author(s): Kazuyoshi Ishii, Shosaku Nomura, Shinya Fujita, Atushi Satake, Tomoki Ito, Yuta Katayama, Taiichi Kyo, Shuichi Ota, Masanori Seki, Shigeru Chiba, Yoshinobu Maeda, Mitsune Tanimoto, Takayuki Ikezoe, Hideo Yagi, Kunio Hayashi, Yoji Ishida, Naohito Fujishima, Kenichi Sawada, Masaya Okada, and Hiroyasu Ogawa,
  • Organizer: 57th Annual Meeting of America Society of Hematology
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2015-12-07
  • Int'l Joint Research
• [Presentation] Platelet Progenitors after Leaving Bone Marrow (2015)
  • Author(s): Shugo Kowata, Ryo Togawa, Yoshiaki Okano, Sumio Isogai, Jiro Hitomi, Kazunori Murai, Shigeki Ito, Yoji Ishida,
  • Organizer: 57th Annual Meeting of America Society of Hematology
  • Place of Presentation: Orland, FL, USA
  • Year and Date: 2015-12-06
  • Int'l Joint Research
• [Presentation] Platelet Progenitors after Leaving Bone Marrow (2015)
  • Author(s): Kowata S, Murai K, Oyake T, Ito S, Ishida Y
  • Organizer: 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11 – 2015-06-14
  • Int'l Joint Research
• [Presentation] Comparison of micafungin and liposome amphotericin B for empirical anti fungal therapy in febrile neutropenic patients with hematological malignancies: A randomized controlled study (2015)
  • Author(s): Fujisawa Y, Oyake T, Sugawara N, Sasaki R, Tsukushi Y, Hanamura I, Fujishima Y, Aoki Y, Kowata S, Ito S, Ishida Y
  • Organizer: 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11 – 2015-06-14
  • Int'l Joint Research
• [Presentation] Doripenemu versus meropenem as the first-line mono-therapy in high risk febrile neutropenic patients with acute leukemia : A randomized, controlled study (2015)
  • Author(s): Sugawara N, Oyake T, Fujisawa Y, Sasaki R, Mine T, Tsukushi Y, Hanamura I, Asahi M, Suzuki Y, Okano Y, Fijishima Y, Aoki Y, Kowata S, Ito S, Ishida Y
  • Organizer: 20th Congress of the European Hematology Association
  • Place of Presentation: Vienna, Austria
  • Year and Date: 2015-06-11 – 2015-06-14
  • Int'l Joint Research