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Functional priming of inflammatory cells and modulation of their apoptosis: significance of these events in children's diseases

Research Project

Project/Area Number 12670738
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionShinshu University School of Medicine

Principal Investigator

YASUI Kozo  Shinshu University, School of Medicine, Associate Professor, 医学部・小児科, 助教授 (90200493)

Co-Investigator(Kenkyū-buntansha) AGEMATSU Kazunaga  Shinshu University, School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (60262721)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsneutrophils / inflammation / signal transduction / monocytes / apoptosis / bronchial asthma / theophylline / 気管支喘息 / 気道炎症 / アデノシン / プロテアーゼインヒビター / PI3キナーゼ
Research Abstract

The unnecessary prolongation of granulocyte life and augmentation of bactericidal ability may produce toxic substances such as leukotrienes and superoxide. Activation of neutrophils ( PMN ) play key roles in systemic inflammation such as that associated with sepsis and ischemia-reperfusion injury. The regulation of cellular apoptosis and the release of toxic substances has been proposed as a key mechanism for the inhibition of inflammatory disease and tissue damage. For example, persistent inflammation in the airways is thought to be an essential feature of bronchial asthma. Histological and bronchoalveolar lavage ( BAL ) fluid studies have demonstrated that inflammatory cell infiltration exists in the airway even in cases of mild asthma, and that this cell population increases in number during severe attacks. It is well-known that neutrophils are frequently more dominant than eosinophils as the major inflammatory cells in sputa from asthmatic patients during acute exacerbation and from those with sudden onset fatal asthma attack. The presence of neutrophil elastase ( NE ) in fluids in the epithelial lining of the airway has been reported to induce further inflammatory cytokine release ( IL-8, GM CSF ) and destroy structures of the extracellular matrix ( ECM ). NE is quickly inactivated by inter- α -trypsin inhibitor ( α_2 macroglobulin ) in vivo. During this process, inter- α -trypsin inhibitor is metabolized to detectable serum trypsin inhibitor ( STI ), which could also potentially inhibit the activity of NE, thus forming a homeostatic negative feedback loop. We speculated that STI may be more dominant in patients with acute asthmatic exacerbation. Since little is known about inflammatory reactions in the airways in childhood asthma, we examined the serum levels of MMP-2, TIMP 1, NE and STI in children with acute asthma exacerbation.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] 安井耕三: "喘息症状の軽快に伴い睡眠障害に改善がみられた小児気管支喘息の1例"小児科診療. 63. 467-469 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安井耕三, 小宮山淳: "SIRSの抗サイトカイン療法"小児内科. 32. 1156-1159 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安井耕三: "顆粒球輸注,感染症"小児科. 41. 1136-1140 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安井耕三: "小児の不明熱とリウマチ性疾患"Progress in Medicine. 21. 865-867 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安井耕三: "小児リウマチ性疾患とTh1/Th2バランス,サイトカイン"小児内科. 33. 774-777 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安井耕三: "抗炎症性サイトカイン療法の臨床"小児科. 42. 1406-1410 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui K et al.: "Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism"J Leukoc Biol. 67. 529-535 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sawai T et al.: "Thrombopoletin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia"J Leukoc Biol. 68. 137-143 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui K et al.: "Theophylline's effects on human eosinophil functions : comparative study with neutrophil functions"J Leukoc Biol. 68. 194-200 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui K, Komiyama A: "Roles of phosphatidylinositol 3-kinase and phospholipase D in temporal activation for superoxide production in FMLP-stimulated human neutrophils"Cell Biochem Funct. 19. 43-50 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinozaki K, Yasui K et al.: "Direct B/B-cell interactions in immunoglobulin synthesis"Clin Exp Immunol. 124. 386-391 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mwamtemi H et al.: "An increase in circulating mast cell colony forming cells in asthma"J Immunol. 166. 4672-4677 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui K, Komiyma A: "New clinical applications of xanthine derivatives : Modulatory actions on leukocyte survival and functions"Int J Hematol. 73. 87-92 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagumo H et al.: "The different process of class switching and somatic hypermutation ; a novel analysis by CD 27 (-) naive B cells"Blood. 99. 567-575 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada S, Yasui K et al.: "Detection of neutrophil associated immunoglobulin (NAIg) using flow cytometry in autoimmune neutropenia in infancy"Pediatr Int. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinozaki K, Yasui K et al.: "Familial mediterranean fever in two Japanese families"J Rheumatol. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui,K., Agematsu,K, Shinozaki,K, Hokibara,S, Nagumo,H., Nakazawa,T., Komiyama,A.: "Theophylline induces neutrophilapoptosis through adenosine A ( 2A ) receptor antagonism"J Leukoc Biol. 67. 529-535 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sawai,T., Koike,K., Mwamtemi,HH. Ito,S., Kurokawa,K., Sakashita,K., Kinoshita,T., Higuchi,T., Takeuchi,K., Shiohara,M., Kamijo,T., Higuchi,Y., Miyazaki,H., Kobayashi,M., Miyake,M., Yasui,K., Komiyama,A.: "Thrombopoetin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia"J Leukoc Biol. 68. 137-143 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui,K., Agematsu,K., Shinozaki,K., Hokibara,S., Nagumo,H., Yamada,S., Kobayashi,N., Komiyama,A.: "Theophylline's effects on human eosin functions: comparative study with neutrophil functions"J Leukoc Biol. 68. 194-200 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui,K., Komiyama,A.: "Roles of phosphatidylinositol 3-kinase and phosphorous D in temporal activation for superoxide production in FMLP-stimulated human neutrophis"J Leukoc Biol. 68. 194-200 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinozaki,K., Yasui,K., Agematsu,K.: "Direct B/B-cell interaction immunoglobulin synthesis"Clin Exp Immunol. 124. 386-391 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Mwamtemi,HH., Koike,K., Kinoshita,T., Ito,S., Ishida,S., Nakazawa,Y., Kurokawa,Y., Shinozaki,K., Sakashita,K., Takeuchi,K., Shiohara,M., Kamijo,T., Yasui,K., Kawano,K., Miyazaki,H., Kato,T., Sakuma,S., Komiyama,A.: "An increase in circulating mast cell colony-forming cells in asthma"J Immunol. 166. 4672-4677 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yasui,K., Komiyama,A.: "New clinical applications of xanthine derived Modulatory actions on leukocyte survival and functions"Int J Hematol. 73. 87-92 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Nagumo,H., Agematsu,K., Kobayashi,N., Shinozaki,K., Hokibara,S., Takamoto,M., Yasui,K., Suagane,K., Komiyama,A.: "The different process of switching and somatic hypermutation; a novel analysis by CD 27 ( - ) naive B cells"Blood. 99. 567-575 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada,S., Yasui,K., Shinozaki,K., Nagumo,H., Kamagai,T.: "Detection of neu associated immunoglobulin ( NAIg ) using flow cytometry in autoimmune neutropenia in infancy."Pediatr Int. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shinozaki,K., Yasui,K., Agematsu,K. Nagumo,H., Naitoh,H., Naganuma, Komiyama,A.: "Familial mediterranean fever in two Japanese families"J Rheumatol. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] 安井耕三: "喘息症状の軽快に伴い睡眠障害に改善がみられた小児気管支喘息の1例"小児科診療. 63. 467-469 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安井耕三, 小宮山淳: "SIRSの抗サイトカイン療法"小児内科. 32. 1156-1159 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安井耕三: "顆粒球輸注,感染症"小児科. 41. 1136-1140 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安井耕三: "小児の不明熱とリウマチ性疾患"Progress in Medicine. 21. 865-867 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安井耕三: "小児リウマチ性疾患とTh1/Th2バランス,サイトカイン"小児内科. 33. 774-777 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 安井耕三: "抗炎症性サイトカイン療法の臨床"小児科. 42. 1406-1410 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui K et al.: "Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism"J Leukoc Biol. 67. 529-535 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sawai T et al.: "Thrombopoietin enhances neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia"J Leukoc Biol. 68. 137-143 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui K et al.: "Theophylline's effects on human eosinophil functions : comparative study with neutrophil functions"J Leukoc Biol. 68. 194-200 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui K, Komiyama A: "Roles of phosphatidylinositol 3-kinase and phospholipase D in temporal activation for superoxide production in FMLP-stimulated human neutrophils"Cell Biochem Funct. 19. 43-50 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinozaki K, Yasui K et al.: "Direct B/B-cell interactions in immunoglobulin synthesis"Clin Exp Immunol. 124. 386-391 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Mwamtemi H et al.: "An increase in circulating mast cell colony forming cells in asthma"J Immunol. 166. 4672-4677 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui K, Komiyama A: "New clinical applications of xanthine derivatives : Modulatory actions on leukocyte survival and functions"Int J Hematol. 73. 87-92 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Nagumo H et al.: "The different process of class switching and somatic hypermutation ; a novel analysis by CD 27 (-) naive B cells"Blood. 99. 567-575 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada S, Yasui K et al.: "Detection of neutrophil associated immunoglobulin (NAlg) using flow cytometry in autoimmune neutropenia in infancy"Pediatr Int. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Shinozaki K, Yasui K et al.: "Familial mediterranean fever in two Japanese families"J Rheumatol. (in press). (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yasui K,Agematsu K, et al.: "Theophylline induces neutrophil apoptosis through adenosine A2A receptor antagonism."J Leukoc Biol. 67. 529-535 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasui K,Agematsu K, et al.: "Theophylline's effects on human eosinophil functions : comparative study with neutrophil functions."J Leukoc Biol. 68. 194-200 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sawai T,Yasui K, et al.: "Thrombopoietin enhancec neutrophil production by bone marrow hematopoietic progenitors with the aid of stem cell factor in congenital neutropenia."J Leukoc Biol. 68. 137-143 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasui K,Komiyama A: "New clinical applications of xanthine derivatives : Modulatory actions on leukocyte survival and functions."Int J Hematol. 73. 87-92 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Yasui K,,Komiyama A: "Roles of phosphatidylinositol 3-kinase and phospholipase D in temporal activation of superoxide production in FMLP-stimulated human neutrophils."Cell Biochem Funct. 19. 43-50 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] 安井耕三,小宮山淳: "SIRSの抗サイトカイン療法"小児内科. 32(8). 1156-1159 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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