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Why does the autoantibody against cytokine incease in patients with idiopathic pulmonary alveolar proteinosis?

Research Project

Project/Area Number 18390240
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionNiigata University

Principal Investigator

NAKATA Koh  Niigata University, Medical and Dental Hospital, professor (80207802)

Co-Investigator(Kenkyū-buntansha) INOUE Yoshikazu  Niigata University, International Medical Center of Japan, 研究部長 (90240895)
NAKAGAKI Kazuhide  Nippon Veterinary and Life Science University, 獣医学部, associate professor (90143635)
TAZAWA Ryushi  Niigata University, Medical and Dental Hospital, Lecturer (70301041)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,940,000 (Direct Cost: ¥15,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2006: ¥12,000,000 (Direct Cost: ¥12,000,000)
Keywordspulmonary alveolar proteinosis / granulocyte macrophage colony stimulating factor / alveolar macrophage / lung surfactant / bronchoalveolar lavage / autoantibody / cytokine / autoimmune disease / ケモカイン / 原発性肺胞蛋白症 / 免疫複合体
Research Abstract

Recent studies have revealed that neutrophils from PAP patients had reduced basal functions such as phagocytosis, cell-adhesion, H_2O_2 production, and microbial killing (Uchida, et. Al.. NEJM.2007). In contrast, we found that some subsets of peripheral blood T and B cells were activated or excessively matured compared to normal controls. In CD4^+ cells, the number of naive T cells was reduced and the effecter-memory/naive ratio was up-regulated. Interestingly, small amount of CD4^+ cells were proliferating ex vivo without any stimulation. In B cells, CD38^+ activated cells were increased in both naive and memory B cell subset, whereas the expression of CD19 was reduced compared to the controls. Cells expressing CD138, a plasma cell marker, were significantly increased. Importantly, GM-CSF autoantibody was detected in the culture supernatants of peripheral blood mononuclear cells after 2 days incubation without any stimulation. These results suggested that some subsets of T and B cells were driven to be matured/activated and possibly promoted to produce the autoantibody.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (27 results)

All 2008 2007 2006 Other

All Journal Article (16 results) (of which Peer Reviewed: 7 results) Presentation (6 results) Book (3 results) Remarks (2 results)

  • [Journal Article] Pulmonary Mycobacterium avium complex infection:Association with NRAMP1 polymorphisms.2007

    • Author(s)
      Tanaka G, Shojima J, Matsushita I, Nagai H, Kurashima A, Nakata K, Toyota E, Kobayashi N, Kudo K, Keicho N.
    • Journal Title

      Eur Respir J. 30

      Pages: 90-96

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Expression of PU.1 and terminal differentiation of alveolar macrophages in newborn rats.2007

    • Author(s)
      Iwabuchi H, Kawasaki T, Yamamoto T, Uchiyama M, Nakata K, Naito M.
    • Journal Title

      Cell Tissue Res. 329(1)

      Pages: 71-79

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Mechanisms of polymorphonuclear neutrophil-mediated induction of HIV-1 replication in macrophages during pulmonary tuberculosis.2007

    • Author(s)
      Hoshino Y, Hoshino S, Gold JA, Raju B, Prabhakar S, Pine R, Rom WN, Nakata K, Weiden M.
    • Journal Title

      J Infect Dis. 195(9)

      Pages: 1303-1310

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Anti-cytokine autoantibodies are ubiquitous in healthy individuals.2007

    • Author(s)
      Watanabe M, Uchida K, Nakagaki K, Kanazawa H, Trapnell B. C., Hoshino Y, Kagamu H, Yoshizawa H, Keicho N, Goto H, and Nakata K.
    • Journal Title

      FEBS Letters 581(10)

      Pages: 2017-2021

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A survey of tuberculosis prevalence in Hanoi, Vietnam.2007

    • Author(s)
      Horie T, Lien LT, Tuan LA, Tuan PL, Sakurada S, Yanai H, Keicho N, Nakata K.
    • Journal Title

      Int J Tuberc Lung Dis. 11(5)

      Pages: 562-566

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Pulmonary Mycobacterium avium complex infection: Association with NRAMP 1 polymorphisms2007

    • Author(s)
      Tanaka, G., Shojima, J., Matsushita, I., Nagai, H., Kurashima, A. Nakata, K., Toyota, E., Kobayashi, N,. Kudo, K., Keicho, N
    • Journal Title

      Eur Respir J 30

      Pages: 90-96

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Expression of PU.1 and terminal differentiation of alveolar macrophages in newborn rats2007

    • Author(s)
      Iwabuchi, H., Kawasaki, T., Yamamoto, T., Uchiyama, M., Nakata, K., Naito, M
    • Journal Title

      Cell Tissue Res 329(1)

      Pages: 71-79

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Mechanisms of polymorphonuclear neutrophil-mediated induction of HIV-1 replication in macrophages during pulmonary tuberculosis2007

    • Author(s)
      Hoshino, Y., Hoshino, S., Gold, JA. Raju, B., Prabhakar, S., Pine, R., Rom, WN., Nakata, K., Weiden, M
    • Journal Title

      J Infect Dis 195(9)

      Pages: 1303-1310

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Anti-cytokine autoantibodies are ubiquitous in healthy individuals2007

    • Author(s)
      Watanabe, M., Uchida, K., Nakagaki, K., Kanazawa, H., Trapnell, B.C., Hoshino, Y., Kagamu, H., Yoshizawa, H., Keicho, N., Goto, H., Nakata, K
    • Journal Title

      FEBS Letters 581(10)

      Pages: 2017-2021

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A survey of tuberculosis prevalence in Hanoi, Vietnam2007

    • Author(s)
      Horie, T., Lien, LT., Tuan, LA. Tuan, PL., Sakurada, S., Yanai, H., Keicho, N., Nakata, K
    • Journal Title

      Int J Tuberc Lung Dis 11(5)

      Pages: 562-566

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Pulmonary Mycobacterium avium complex infection: Association with NRAMP1 polymorphisms.2007

    • Author(s)
      Tanaka G, Shojima J, Matsushita I, Nagai H, Kurashima A, Nakata K, Toyota E, Kobayashi N, Kudo K, Keicho N.
    • Journal Title

      Eur Respir J. 30

      Pages: 90-96

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Anti-cytokine autoantibodies are ubiquitous in healthy individuals.2007

    • Author(s)
      . Watanabe M, Uchida K, Nakagaki K, Kanazawa H, Trapnell B. C., Hoshino Y, Kagamu H, Yoshizawa H, Keicho N, Goto H, and Nakata K.
    • Journal Title

      FEBS Letters 581(10)

      Pages: 2017-2021

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanisms of PMN-Mediated Induction of HIV-1 Replication in Macrophages during Pulmonary Tuberculosis2007

    • Author(s)
      Yoshihiko Hoshino, et al.
    • Journal Title

      The Journal of Infictious Diseases (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] pulmonary alveolar proteinosis and anti-GM-CSF antibody2006

    • Author(s)
      Watanabe M, Nakata K
    • Journal Title

      Nippon Naikagakkaishi 95

      Pages: 1042-1042

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Serum Antibody Against Granulocyte/Macrophage Colony-Stimulating Factor and KL-6 in Idiopathic Pulmonary Alveolar Proteinosis2006

    • Author(s)
      Masayuki Nara, et al.
    • Journal Title

      The Tohoku Joumal of Experimental Medicine Vol. 208 (2006),N0. 4 pp.349-354 208

      Pages: 349-354

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Outbreak of Nocardia farcinica infection with the same pattern in randomly amplified polymorphic DNA analysis.2006

    • Author(s)
      Kachi S, et al.
    • Journal Title

      J Hosp Infect. 2006 Apr;62(4) : 502-6. Epub 2006 Feb 17. 62(4)

      Pages: 502-6

    • Related Report
      2006 Annual Research Report
  • [Presentation] プラズマ放電を用いた細胞プロセッシングシステム構築の可能性について2008

    • Author(s)
      中田 光
    • Organizer
      第7回日本再生医療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2008-03-13
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] GM-CSF欠損マウス、GM-CSF過剰産生マウスの気管支肺胞洗浄液(BALF)のプロテオーム解析2007

    • Author(s)
      中田 光
    • Organizer
      臨床プロテオーム研究会
    • Place of Presentation
      東京
    • Year and Date
      2007-12-18
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Multicenter Phase II Trial of Inhaled Aerosolized GM-CSF Therapy for PAP in Japan2007

    • Author(s)
      Nakata, Koh
    • Organizer
      American Thoracic Society International Conference, Symposium
    • Place of Presentation
      San Francisco
    • Year and Date
      2007-05-20
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 招待講演:肺胞蛋白症はどこまで明らかとなったか?2007

    • Author(s)
      中田 光
    • Organizer
      第47回日本呼吸器学会学術講演会個別化医療講演
    • Place of Presentation
      東京
    • Year and Date
      2007-05-10
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] Rational for the novel classification of PAP2007

    • Author(s)
      Nakata, Koh
    • Organizer
      Fifth Annual International Pulmonary Alveolar Proteinosis Scientific Conference
    • Place of Presentation
      大阪
    • Year and Date
      2007-05-08
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 肺胞タンパク症のブレイクスルー2007

    • Author(s)
      中田 光
    • Organizer
      第112回日本解剖学会招待講演
    • Place of Presentation
      大阪
    • Year and Date
      2007-03-06
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 今日の診断基準2007

    • Author(s)
      泉 信有, 中田 光
    • Total Pages
      118
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 呼吸器疾患最新の治療2007-20092007

    • Author(s)
      大橋和政, 中田 光
    • Total Pages
      506
    • Publisher
      南江堂
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Book] 内科学2006

    • Author(s)
      中田 光, ほか 監修 金渾一郎, 北原光夫, 山口徹, 小俣正男
    • Total Pages
      2994
    • Publisher
      医学書院
    • Related Report
      2006 Annual Research Report
  • [Remarks] 「研究成果報告書概要(和文)」より

    • URL

      http://www.bmrctr.jp/

    • Related Report
      2007 Final Research Report Summary
  • [Remarks]

    • URL

      http://www.bmrctr.jp/

    • Related Report
      2007 Annual Research Report

URL: 

Published: 2006-04-01   Modified: 2021-12-20  

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