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Pharmacokinetics of phagocytes in phagocyte disorders

Research Project

Project/Area Number 18K07807
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionNational Center for Child Health and Development

Principal Investigator

Kawai Toshinao  国立研究開発法人国立成育医療研究センター, 生体防御系内科部, 医長 (20328305)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords好中球 / 食細胞 / 遊走能 / 食細胞機能異常症 / 慢性肉芽腫症 / 殺菌能 / 原発性免疫不全症
Outline of Final Research Achievements

Phagocytes play central role in innate immunity, which are characterized by various functions including phagocytosis, production of reactive oxygen species, release of granule component and migration. The observation and continuous recording of phagocytic function can lead to assess the pharmacokinetics of phagocytes. In this study, we demonstrated the migration of neutrophils in response to the chemotactic factors.
Wiscott-Aldrich syndrome (WAS) is immunodeficiency disorder, characterized by the dysfunction of the dynamic remodelling of the actin-based cytoskeleton in migration. The neutrophil of WAS demonstrated less ability of migration. Chronic granulomatous disease (CGD) is characterized by a functional disorder of phagocytes to produce reactive oxygen species. In CGD, the migration of neutrophils in response to the chemotactic factors demonstrated the speed and acceleration similar to that of healthy control, however, CGD neutrophils migrated with multi-direction.

Academic Significance and Societal Importance of the Research Achievements

本研究では、微小空間に化学物質の安定的な濃度勾配を形成し、化学物質に対する細胞の反応をリアルタイムに観察可能なライブイメージング技術を用いて、細胞動態を検討した。
慢性肉芽腫症は、食細胞の殺菌能が低下する原発性免疫不全症であるが、本疾患でみられる易感染性や過剰炎症などの機序について、不明な点が残されている。従来のボイデンチャンバー法では、遊走した細胞数を測定するだけの評価であった。しかし、本研究では、遊走の過程を画像的に解析することで、本疾患の好中球は様々に蛇行を繰り返して進むことが明らかになった。本解析は、他の食細胞機能異常症にも応用できる可能性があり、病態解明へ貢献し得ると考える。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (16 results)

All 2021 2020 2019 2018

All Journal Article (8 results) (of which Peer Reviewed: 5 results) Presentation (4 results) (of which Invited: 1 results) Book (4 results)

  • [Journal Article] Ecthyma gangrenosum in an infant with neutropenia.2021

    • Author(s)
      Kikuchi N, Nakao H, Matsumoto Y, Yoshida K, Okai M, Kawai T, Kubota M, Ishiguro A.
    • Journal Title

      Int J Hematol.

      Volume: 113 Issue: 1 Pages: 3-4

    • DOI

      10.1007/s12185-020-03037-y

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bacillus Calmette-Gu?rin (BCG) Infections at High Frequency in Both AR-CGD and X-CGD Patients Following BCG Vaccination2020

    • Author(s)
      Ishikawa Takashi、Okai Masashi、Mochizuki Emi、Uchiyama Toru、Onodera Masafumi、Kawai Toshinao
    • Journal Title

      Clinical Infectious Diseases

      Volume: - Issue: 9 Pages: e2538-e2544

    • DOI

      10.1093/cid/ciaa1049

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prospective Study of Allogeneic Hematopoietic Stem Cell Transplantation with Post-Transplantation Cyclophosphamide and Antithymocyte Globulin from HLA-Mismatched Related Donors for Nonmalignant Diseases2020

    • Author(s)
      Osumi T、Yoshimura S、Sako M、Uchiyama T、Ishikawa T、Kawai T、Inoue E、Takimoto T、Takeuchi I、Yamada M、Sakamoto K、Yoshida K、Kimura Y、Matsukawa Y、Matsumoto K、Imadome K、Arai K、Deguchi T、Imai K、Yuza Y、Matsumoto K、Onodera M、Kanegane H、Tomizawa D、Kato M
    • Journal Title

      Biology of Blood and Marrow Transplantation

      Volume: 26 Issue: 11 Pages: e286-e291

    • DOI

      10.1016/j.bbmt.2020.08.008

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A prospective study of allogeneic transplantation from unrelated donors for chronic granulomatous disease with target busulfan-based reduced-intensity conditioning.2019

    • Author(s)
      Osumi T, Tomizawa D, Kawai T, Sako M, Inoue E, Takimoto T, Tamura E, Uchiyama T, Imadome K, Taniguchi M, Shirai R, Yoshida M, Ando R, Tsumura Y, Fuji H, Matsumoto K, Shioda Y, Kiyotani C, Terashima K, Onodera M, Matsumoto K, Kato M
    • Journal Title

      Bone Marrow Transplant.

      Volume: 54 Issue: 1 Pages: 168-172

    • DOI

      10.1038/s41409-018-0271-9

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Thymitis in chronic granulomatous disease2019

    • Author(s)
      Kanamori K, Tamura E, Onodera M, Ishiguro A, Kawai T.
    • Journal Title

      Pediatr Int.

      Volume: 61 Issue: 4 Pages: 429-431

    • DOI

      10.1111/ped.13810

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Multiple osteolytic lesions on the skull of a girl with MSMD.2018

    • Author(s)
      Shoji K, Kawai T, Onodera M, Tsutsumi Y, Nosaka S, Miyairi I
    • Journal Title

      Pediatr Int.

      Volume: 60 Issue: 11 Pages: 1043-1044

    • DOI

      10.1111/ped.13691

    • Related Report
      2018 Research-status Report
  • [Journal Article] 食細胞機能異常症2018

    • Author(s)
      河合利尚
    • Journal Title

      小児科診療

      Volume: 81 Pages: 228-231

    • Related Report
      2018 Research-status Report
  • [Journal Article] 食細胞機能異常症2018

    • Author(s)
      河合利尚
    • Journal Title

      小児内科

      Volume: 50 Pages: 262-263

    • Related Report
      2018 Research-status Report
  • [Presentation] 造血幹細胞を標的とした遺伝子治療2020

    • Author(s)
      河合利尚
    • Organizer
      第143回日本薬理学会関東部会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] 食細胞の減少・機能異常で知っておきたいこと2019

    • Author(s)
      河合利尚
    • Organizer
      日本免疫不全・自己炎症学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 小児期から重症感染症を繰り返すX連鎖性慢性肉芽腫症の成人女性例2018

    • Author(s)
      石川尊士、田村英一郎、内山徹、小野寺雅史、和田靖之、河合利尚
    • Organizer
      小児感染症学会
    • Related Report
      2018 Research-status Report
  • [Presentation] Coadministration of thalidomide ameliorates inflammatory bowel disease associated with chronic granulomatous disease.2018

    • Author(s)
      Kawai T, Arai K, Ishikawa T, Tamura E, Uchiyama T, Onodera M
    • Organizer
      European Society of Immunodeficiency diseases
    • Related Report
      2018 Research-status Report
  • [Book] 小児感染免疫学 ~慢性肉芽腫症~2020

    • Author(s)
      河合利尚
    • Total Pages
      2
    • Publisher
      朝倉書店
    • Related Report
      2020 Annual Research Report
  • [Book] 消化器病学サイエンス~慢性肉芽腫症関連腸炎とはどのようなものか~2020

    • Author(s)
      河合利尚
    • Total Pages
      4
    • Publisher
      先端医学社
    • Related Report
      2020 Annual Research Report
  • [Book] 小児感染免疫学 ~感染と生体防御~2020

    • Author(s)
      河合利尚
    • Total Pages
      4
    • Publisher
      朝倉書店
    • Related Report
      2020 Annual Research Report
  • [Book] 小児臨床検査マニュアル 原発性免疫不全症2020

    • Author(s)
      河合利尚
    • Total Pages
      2
    • Publisher
      診断と治療社
    • Related Report
      2019 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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