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Analysis of a mechanism of neutrophil extracellular trap (NET) fromation and a role of NETs in infectious and inflammatory diseases.

Research Project

Project/Area Number 23591474
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Infectious disease medicine
Research InstitutionKyoto University

Principal Investigator

YAMASHITA KOUHEI  京都大学, 医学(系)研究科(研究院), 講師 (80402858)

Project Period (FY) 2011 – 2013
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords好中球細胞外トラップ / NADPH oxidase / 一重項酸素 / 血栓性微小血管障害 / 造血幹細胞移植 / 高尿酸血症 / 心血管障害 / 殺菌 / 好中球 / 細胞外トラップ / 血管内皮細胞障害 / 同種造血細胞移植 / IgG4関連疾患 / 微小血管障害 / 活性酸素 / 慢性肉芽腫症
Research Abstract

Neutrophil extracellular traps (NETs), a newly recognized extracellular killing mechanism by activated neutrophils, contribute to host defense, however, it is reported to be relevant to the pathogenesis of immunothrombosis and inflammatory/ autoimmune diseases by releasing potent hazarous mediators, such as anti-microbial peptides. In this study, we revealed three major findings as below; 1) Siglet oxygen, one of the reactive oxygen species produced by activated neutrophils, is essential for NET formation, 2) Serum NET levels predict thrombotic microangiopathy after allogeneic stem cell transplantaion (SCT), which is one of the critical complications of SCT. 3) Uric acid induces NADPH oxidase-independent NET formation, suggesting that NETs could be a missing link between serum uric acid elevation and cardiovascular diseases.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (39 results)

All 2014 2013 2012 2011 Other

All Journal Article (20 results) (of which Peer Reviewed: 19 results,  Open Access: 1 results) Presentation (17 results) Remarks (2 results)

  • [Journal Article] Uric acid induces NADPH oxidase-independent neutrophil extracellular trap formation2014

    • Author(s)
      Arai Y, Nishinaka Y, Arai T, Morita M, Mizugishi K, Adachi S, Takaori-Kondo A, Watanabe T, Yamashita K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 443 Pages: 556-61

    • NAID

      40021104154

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] 好中球の細胞外殺菌機構(NETs)-感染防御における役割と自己免疫・炎症病態への関与-2014

    • Author(s)
      新井康之,山下浩平
    • Journal Title

      炎症と免疫

      Volume: 22 Pages: 122-34

    • Related Report
      2013 Final Research Report
  • [Journal Article] Uric acid induces NADPH oxidase-independent neutrophil extracellular trap formation.2014

    • Author(s)
      Arai Y, Nishinaka Y, Arai T, Morita M, Mizugishi K, Adachi S, Takaori-Kondo A, Watanabe T, Yamashita K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 443 Issue: 2 Pages: 556-561

    • DOI

      10.1016/j.bbrc.2013.12.007

    • NAID

      40021104154

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CKIP-1 Is an Intrinsic Negative Regulator of T-Cell Activation through an Interaction with CARMA1.2014

    • Author(s)
      Sakamoto T, Kobayashi M, Tada K, Shinohara M, Io K, Nagata K, Iwai F, Takiuchi Y, Arai Y, Yamashita K, Shindo K, Kadowaki N, Koyanagi Y, Takaori-Kondo A
    • Journal Title

      PLoS One

      Volume: 9 Issue: 1 Pages: 1-11

    • DOI

      10.1371/journal.pone.0085762

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Serum neutrophil extracellular traps levels predict thrombotic microangiopathy after allogeneic stem cell transplantation2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Watanabe T, Sakamoto S, Kitano T, Kondo T, Kawabata H, Kadowaki N, Takaori-Kondo A
    • Journal Title

      Biol Blood Marrow Transpl

      Volume: 19 Pages: 1683-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced generation of reactive oxygen species by interferon-may have contributed to successful treatment of invasive pulmonary aspergillosis in a patient with chronic granulomatous disease2013

    • Author(s)
      Yamashita K, Miyoshi T, Arai Y, Mizugishi K, Takaori-Kondo A, Ueyama T
    • Journal Title

      Int J Hematol

      Volume: 97 Pages: 505-10

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The implication of myelodysplastic syndrome-associated chromosomal abnormalities in the development of graft-versus-host disease2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Takaori-Kondo A, Chiba T, Watanabe T
    • Journal Title

      Eur J Haematol

      Volume: 90 Pages: 525-30

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Familial Mediterranean fever mutations in a patient with recurrent episodes of acute respiratory distress syndrome2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Watanabe T, Kondo T, Kitano T, Kawabata H, Kadowaki N, Takaori-Kondo A
    • Journal Title

      Clin Immunol

      Volume: 147 Pages: 58-60

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Toll-like receptor activation in basophils contributes to the development of IgG4-related disease2013

    • Author(s)
      Watanabe T, Yamashita K, Sakurai T, Kudo M, Shiokawa M, Uza N, Kodama Y, Uchida K, Okazaki K, Chiba T
    • Journal Title

      J Gastroenterol

      Volume: 48 Pages: 247-53

    • NAID

      10031156310

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] The implication of myelodysplastic syndrome-associated chromosomal abnormalities in the development of graft-versus-host disease.2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Takaori-Kondo A, Chiba T, Watanabe T.
    • Journal Title

      Eur J Haematol

      Volume: 90 Issue: 6 Pages: 525-530

    • DOI

      10.1111/ejh.12100

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Serum neutrophil extracellular traps levels predict thrombotic microangiopathy after allogeneic stem cell transplantation.2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Watanabe T, Sakamoto S, Kitano T, Kondo T, Kawabata H, Kadowaki N, Takaori-Kondo A.
    • Journal Title

      Biol Blood Marrow Transpl

      Volume: 19 Issue: 12 Pages: 1683-1689

    • DOI

      10.1016/j.bbmt.2013.09.005

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Toll-like receptor activation in basophils contributes to the development of IgG4-related disease.2013

    • Author(s)
      Watanabe T, Yamashita K, Sakurai T, et al
    • Journal Title

      J Gastroenterol

      Volume: 48 Issue: 2 Pages: 247-253

    • DOI

      10.1007/s00535-012-0626-8

    • NAID

      10031156310

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Familial Mediterranean fever mutations in a patient with recurrent episodes of acute respiratory distress syndrome.2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Watanabe T, Kondo T, Kitano T, Kawabata H, Kadowaki N, Takaori-Kondo A.
    • Journal Title

      Clin Immunol

      Volume: 147 Issue: 1 Pages: 58-60

    • DOI

      10.1016/j.clim.2013.02.016

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Enhanced generation of reactive oxygen species by interferon-gamma may have contributed to successful treatment of invasive pulmonary aspergillosis in a patient with chronic granulomatous disease.2013

    • Author(s)
      Yamashita K, Miyoshi T, Arai Y, Mizugishi K, Takaori-Kondo A, Ueyama T.
    • Journal Title

      Int J Hematol

      Volume: 97 Issue: 4 Pages: 505-510

    • DOI

      10.1007/s12185-013-1315-y

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Differing impacts of pretransplant serum ferritin and c-reactive protein levels on the incidence of chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation2013

    • Author(s)
      Sakamoto S, Kawabata H, Kanda J, Uchiyama T, Mizumoto C, Kondo T, Yamashita K, Ichinohe T, Ishikawa T, Kadowaki N, Takaori-Kondo A
    • Journal Title

      Int J Hematol

      Volume: 97 Issue: 1 Pages: 109-116

    • DOI

      10.1007/s12185-012-1229-0

    • NAID

      10031144642

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Clinical value of (11)C-methionine PET/CT in patients with plasma cell malignancy: comparison with (18)F-FDG PET/CT2013

    • Author(s)
      Nakamoto Y, et al
    • Journal Title

      Eur J Nucl Med Mol Imaging

      Volume: Vol.40、No.5 Issue: 5 Pages: 708-715

    • DOI

      10.1007/s00259-012-2333-3

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation of toll-like receptors and NOD-like receptors in involved in enhanced IgG4 responses in autoimmune pancreatitis2012

    • Author(s)
      Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa M, Kodama Y, Uchida K, Okazaki K, Chiba T
    • Journal Title

      Arthritis Rheum

      Volume: 64 Pages: 914-24

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Involvement of activation of toll-like receptors and nucleotide-binding oligomerization domain-like receptors in enhanced IgG4 responses in autoimmune pancreatitis.2012

    • Author(s)
      Watanabe T, Yamashita K, Fujikawa S, Sakurai T, Kudo M, Shiokawa M, Kodama Y, Uchida K, Okazaki K, Chiba T.
    • Journal Title

      Arthritis Rheum

      Volume: 64 Pages: 914-924

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Journal Article] Singlet oxygen is essential for neutrophil extracellular trap formation2011

    • Author(s)
      Nishinaka Y, Arai T, Adachi S, Takaori-Kondo A, Yamashita K
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 413 Pages: 75-9

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Singlet oxygen is essential for neutrophil extracellular trap formation.2011

    • Author(s)
      Nishinaka Y, Arai T, Adachi S, Takaori-Kondo A, Yamashita K.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 413 Pages: 75-79

    • Related Report
      2011 Research-status Report
    • Peer Reviewed
  • [Presentation] Uric Acid Induces NADPH Oxidase-Independent Neutrophil Extracellular Trap Formation2013

    • Author(s)
      Arai Y, Nishinaka Y, Arai T, Mizugishi K, Adachi S, Takaori-Kondo A, Yamashita K
    • Organizer
      55th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      New Orleans, USA
    • Year and Date
      2013-12-10
    • Related Report
      2013 Final Research Report
  • [Presentation] Plasmacytoid dendritic cells activated by neutrophil extracellular traps contribute to the pathogenesis of IgG4-related disease2013

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Takaori-Kondo A
    • Organizer
      Annual European Congress of Rheumatology EULAR 2013
    • Place of Presentation
      Madrid, Spain
    • Year and Date
      2013-06-13
    • Related Report
      2013 Final Research Report
  • [Presentation] Serum Neutrophil Extracellular Traps (NETs) Are a Potential Predictive Marker for Thrombotic Microangiopathy (TMA) After Allogeneic Stem Cell Transplantation2012

    • Author(s)
      Arai Y, Sakamoto S, Yamashita K, Mizugishi K, Kitano T, Kondo T, Kawabata H, Kadowaki N, Takaori-Kondo A
    • Organizer
      54th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      Atlanta, USA
    • Year and Date
      2012-12-08
    • Related Report
      2013 Final Research Report
  • [Presentation] A novel role of uric acid in neutrophil extracellular trap formation2012

    • Author(s)
      Nishinaka Y, Arai T, Morita M, Arai Y, Mizugishi K, Adachi S, Takaori-Kondo A, Yamashita K
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2012-10-20
    • Related Report
      2013 Final Research Report
  • [Presentation] 高濃度尿酸によるNADPH oxidase非依存性NETosisの誘導2012

    • Author(s)
      西中瑶子,森田真紀子,荒井俊之,山下浩平,足立壯一
    • Organizer
      第21回日本Cell Death学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      2012-07-28
    • Related Report
      2013 Final Research Report
  • [Presentation] Serum Neutrophil Extracellular Traps (NETs) Are a Potential Predictive Marker for Thrombotic Microangiopathy (TMA) After Allogeneic Stem Cell Transplantation.2012

    • Author(s)
      Arai Y, Sakamoto S, Yamashita K, Mizugishi K, Kitano T, Kondo T, Kawabata H, Kadowaki N, Takaori-Kondo A.
    • Organizer
      54th Annual Meeting of the American Society of Hematology
    • Place of Presentation
      米国Atlanta, Convention Center
    • Related Report
      2012 Research-status Report
  • [Presentation] ARDSを繰り返し発症した,MEFV遺伝子変異を有するMDS/MPNの一例.2012

    • Author(s)
      新井康之, 山下浩平, 水岸貴代美, 近藤忠一, 北野俊行, 川端浩, 高折晃史.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都、国立京都国際会館
    • Related Report
      2012 Research-status Report
  • [Presentation] A novel role of uric acid in neutrophil extracellular trap formation.2012

    • Author(s)
      Nishinaka Y, Arai T, Morita M, Arai Y, Mizugishi K, Adachi S, Takaori-Kondo A, Yamashita K.
    • Organizer
      第74回日本血液学会学術集会
    • Place of Presentation
      京都、国立京都国際会館
    • Related Report
      2012 Research-status Report
  • [Presentation] 高濃度尿酸によるNADPH oxidase非依存性NETosisの誘導.2012

    • Author(s)
      西中 瑶子,森田 真紀子,荒井 俊之,山下 浩平,足立 壯一.
    • Organizer
      第21回日本Cell Death学会学術集会
    • Place of Presentation
      名古屋、名古屋大学医学部付属病院中央診療棟3階講堂
    • Related Report
      2012 Research-status Report
  • [Presentation] リツキシマブ投与後の遅発性好中球減少症に関する検討.2012

    • Author(s)
      新井康之, 山下浩平, 近藤忠一, 高折晃史.
    • Organizer
      第82回日本感染症学会中日本地方会学術集会.
    • Place of Presentation
      福岡、アクロス福岡
    • Related Report
      2012 Research-status Report
  • [Presentation] Singlet oxygen is essential for neutrophil extracellular trap formation2011

    • Author(s)
      Nishinaka Y, Morita M, Arai T, Adachi S, Takaori-Kondo A, Yamashita K
    • Organizer
      The 53^<rd> ASH Annual Meeting and Exposition
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-12-12
    • Related Report
      2013 Final Research Report
  • [Presentation] Singlet oxygen is essential for neutrophil extracellular trap formation2011

    • Author(s)
      Yamashita K, Nishinaka Y, Arai T, adachi S, Takaori-Kondo A
    • Organizer
      第73回日本血液学会総会
    • Place of Presentation
      名古屋
    • Related Report
      2013 Final Research Report
  • [Presentation] Singlet oxygen is essential for neutrophil extracellular trap formation.2011

    • Author(s)
      Yamashita K, Nishinaka Y, Arai T, Adachi S, Takaori-Kondo A.
    • Organizer
      第73回日本血液学会総会
    • Place of Presentation
      名古屋市、名古屋国際会議場
    • Related Report
      2011 Research-status Report
  • [Presentation] Singlet oxygen is essential for neutrophil extracellular trap formation.2011

    • Author(s)
      Nishinaka Y, Morita M, Arai T, Adachi S, Takaori-Kondo A, Yamashita K.
    • Organizer
      53rd ASH Annual Meeting and Exposition
    • Place of Presentation
      米国San Diego, Convention Center
    • Related Report
      2011 Research-status Report
  • [Presentation] Plasmacytoid dendritic cells activated by neutrophil extracellular traps contribute to the pathogenesis of IgG4-related disease.

    • Author(s)
      Arai Y, Yamashita K, Mizugishi K, Takaori-Kondo A.
    • Organizer
      Annual European Congress of Rheumatology EULAR 2013.
    • Place of Presentation
      Madrid, Spain
    • Related Report
      2013 Annual Research Report
  • [Presentation] 同種造血幹細胞移植後の低ガンマグロブリン血症に関する後方視的解析.

    • Author(s)
      新井康之, 山下浩平, 近藤忠一, 北野俊行, 高折晃史.
    • Organizer
      第75回日本血液学会学術集会
    • Place of Presentation
      札幌
    • Related Report
      2013 Annual Research Report
  • [Presentation] Uric Acid Induces NADPH Oxidase-Independent Neutrophil Extracellular Trap Formation.

    • Author(s)
      Arai Y, Nishinaka Y, Arai T, Mizugishi K, Adachi S, Takaori-Kondo A, Yamashita K.
    • Organizer
      55th Annual Meeting of the American Society of Hematology.
    • Place of Presentation
      New Orleans, USA
    • Related Report
      2013 Annual Research Report
  • [Remarks] 京都大学大学院医学研究科 血液・腫瘍内科学 生体防御研究

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/biophylaxis.html

    • Related Report
      2013 Final Research Report
  • [Remarks] 京都大学大学院医学研究科 血液・腫瘍内科学 生体防御研究室

    • URL

      http://www.kuhp.kyoto-u.ac.jp/~hemonc/research/biophylaxis.html

    • Related Report
      2012 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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