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Prevention of normal tissue damage caused by primed neutrophils under the control of intracellular signal transduction

Research Project

Project/Area Number 09670797
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionSHINSHU UNIVERSITY

Principal Investigator

YASUI Kozo  Shinshu Univ.Hosp.Pediatrics, Lecturer, 医学部・附属病院, 講師 (90200493)

Co-Investigator(Kenkyū-buntansha) AGEMATSU Kazunaga  Shinshu Univ.Sch.Med.Ped., Lecturer, 医学部, 講師 (60262721)
松岡 高史  信州大学, 医療技術短期大学部, 助教授 (70270965)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1998: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1997: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywordsneutrophils / eosinophils / GM-CSF / apoptosis / theophylline / Down syndrome / pentoxifylline / Behcet disease / 好酸球f / アポートーシス / 食細胞 / 細胞内情報伝達 / 炎症 / 喘息 / 活性酸素
Research Abstract

In iniflammatory sites, GM-CSF is mainly produced by macrophages and activated T cells. The inflammatory site is surrounded by macrophages and T cells, which are called satelite cells. Bactericidal ability of neutrophils is augmented and the cellular survival is prolonged by the treatment of GM-CSF.In contrast, G-CSF has a weaker effect, G-CSF is mainly produced by epithelium or fibroblast in stromal cells. The lower concentrations of GM-CSF enhance neutrophil chemotaxis, meanwhile the higher concentrations of GM-CSF induce the tight regulation of integrin adhesiveness and the specific localization of activated neutrophils to inflammatory sites. From these findings, GM-CSF is supposed to play as a pro-inflammatory cytokine in several diseases as ARDS and bronchial asthma.
The unnecessary prolongation of neutrophil and augmentation of bactericidal ability may produce toxic substances. The regulation of granulocyte life and function has been proposed as a key mechanism for the inhibition … More of inflammatory disease and tissue damage. In bronchial asthma, cytokines as GM-CSF and IL-5 are upregulated and have been proposed to cause granulocyte infilitration in the airway. We examined the abilities of theophylline, a brochodilator, to counteract the prolongation of human granulocyte survival caused by GM-CSF and IL-5. Theophylline's effect to accelerate granulocyte apoptosis is an important immunomodulatory action in the control of bronchial asthma. In addition, we examined neutrophil apoptosis in individuals with Down syndrome (DS). Granulocyte survival is shortened in DS individuals, accerelated apoptosis of granulocytes may be a factor to prevent chronic airway inflammation and bronchial asthma in DS.The superoxide dismutase gene resides on chromosome 21, SOD may be a key enzyme in the mechanism to induce cellular apoptosis.
Behcet disease is a chronic condition in which the functions of neutrophils are characteristically increased. We examined the effect of pentoxifylline (a membrane fluidizer) in controlling Behcet disease, and further studies have been done between children's cases. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (75 results)

All Other

All Publications (75 results)

  • [Publications] 安井耕三,小宮山淳: "Chediak-Higashi症候群の責任遺伝子." 医学のあゆみ. 180. 510-511 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "好中球機能発現における細胞内情報伝達機構." 炎症. 17. 231-237 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "先天性遺伝性食細胞機能異常症のmolecularbasisについての最近の知見" 日臨免誌. 20. 145-151 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "Chediak-Higashi症候群発症遺伝子の同定." 臨床免疫. 29. 1016-1019 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "Chediak-東症候群における責任蛋白質." 医学のあゆみ. 182. 767-770 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三,小宮山淳: "小児の好中球減少症" 日常診療と血液. 7. 1561-1566 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "好中球のシグナル伝達." 炎症と免疫. 6. 63-70 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 桐麻由美,安井耕三他: "アスペルギルス肺炎の浸潤により脊髄麻痺をきたした慢性肉芽腫症の1例." 小児内科. 30. 561-566 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 大賀正一,安井耕三他: "顆粒球輸血の考え方-アンケート調査の結果から-." 小児感染免疫. 10. 37-44 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "好中球機能発現と細胞内情報伝達." 小児感染免疫. 10. 105-110 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 水亜矢子,安井耕三他: "Pentoxifyllineを加えた3剤併用治療法が奏功した腸管型Behcet病の小児例" 小児科診療. 61. 1182-1185 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "免疫不全症候群" 小児看護. 21. 1217-1220 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hu B,Yasui K.: "Effects of colony-stimulating factors(CSFs)on neutrophil apoptosis" Int J Hematol. 66. 179-188 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K et al.: "Treatment of Behcet disease with pentoxifylline" Ann Intern Med. 126. 493-494 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K et al.: "Theophylline accelerates qranulocyte apoptosis not via phosphodiesterase inhibition" J Clin Invest. 100. 1677-1684 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi T,et al.: "Megakaryocytes derived from CD34 Positive cord blood cells produce interleukin-8" Br J Haematol. 99. 509-516 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Agematsu K et al.: "Generation of plasma cells from peripheral blood memory B cells." Blood. 91. 173-180 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinozaki K et al.: "Biphasic effects of granulocyte-macrophage-------" Jpn J Pediacr Hematol. 12. 87-92 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Agematsu K et al.: "Absence of IgD CD27+ memory B cell population in---" J Clin Invest. 102. 87-92 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuoka T et al.: "Defective late phase of respiratory burst --------" Jpn J Obsteric Gynecologic Neonatal Hema. 8. 70-75 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagumo H et al.: "CD27/CD70 interaction augments IgE secretion ------" J Immunol. 161. 6496-6502 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K et al.: "Behcet's disease in children" J Pediatr. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K et al.: "RhG-CSF therapy for sepsis in infants with------" Pediatrics. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K et al.: "Presenility of granulocytes in Down syndrome" Am J Med Genet. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三,小宮山淳: "血液症候群II(別冊日本臨床)好中球ATP欠損症." 日本臨床社, 91-93 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三: "シグナル伝達機構.“好中球-機能低下と機能亢進"" 笹田昌孝編.医薬ジャーナル, 79-93 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Hu B,Yasui K.: "Effects of colony-stimulating factors (CSFs) on neutrophil apoptosis : possible roles in inflammation site." Int J Hematol. 66. 179-188 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K,Ohta K,Komiyama A.: "Treatment of Behcet disease with pentoxifylline" Ann Intern Med. 126. 493-494 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K,Hu B,Nakazawa T,Agematsu K,Komiyama A.: "Theophylline accelerates granulocyte apoptosis not via phosphodiesterase inihibition" J Clin Invest. 100. 1677-1684 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Higuchi T,Koike K,Sawai N,Mwamtemi HH,Takeuchi K,Shiohara M,Kikuchi T,Yasui K,Ito S,Yamaguchi O,Sasaki Y,Okumura N,Kato T,Miyazaki H,Ikeda M,Yamada M,Komiyama A.: "Megakaryocytes derived from CD34-positive cord blood cells produce interleukin-8." Br J Haematol. 99. 509-516 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Agematsu K,Nagumo H,Oguchi Y,Nakazawa T,Fukushima K,Yasui K,Ito S,Kobata T,Morimoto C,Momiyama A.: "Generation of plasma cells from peripheral blood memory B cells : Synergistic effect of interleukin-10 and CD27/CD70 interaction." Blood. 91. 173-180 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Shinozaki K,Yasui K,Komiyama A: "Biphasic effects of granulocyte-macrophage colony-stimulating factor on neutrophil chemotaxis with changes in the expression of CR3 adhesion molecule" Jpn J Pediatr Hematol. 12. 87-92 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Agematsu K,Nagumo H,Shinozaki K,Hokibara S,Yasui K,Terada K,Kawamura N,Toba T,Nonoyama S,Ochs HD,Komiyama A.: "Absence of IgD-CD27^+ memory B cell population in X-linked Hyper-IgM syndrome" J Clin Invest. 102. 853-860 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Matsuoka T,Tamaki H,Yoda T,Yamazaki M,Yasui K,Komiyama A.: "Defective late phase of respiratory burst despite increased superoxide anion release in neonatal polymorphonuclear leukocytes : Impaired myeloperoxidase release as a probable cause of the abnormality" Jpn J Obsteric Gynecologic Neonatal Hematol. 8. 70-75 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Nagumo H,Agematsu K,Shinozaki K,Hokibara S,Ito S,Takamoto M,Nikaido T,Yasui K,Uehara Y,Yachie A,Komiyama A: "CD27/CD70 interaction augments IgE secretion by promoting the differentiation of memory B cells into plasma cells" J Immunol. 161. 6496-6502 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K,Komiyama A,Takabayashi Y,Fujikawa S.: "Behcet's disease in children" J Pediatr. 134 ; (in press). (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K,Agematsu K,Komiyama A.: "RhG-CSF therapy for sepsis in infants with neutropenia." Pediatrics. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yasui K,Shinozaki K,Nakazawa T,Agematsu K,Komiyama A.: "Presenility of granulocytes in Down syndrome." Am J Med Genet. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] 安井耕三,小宮山敦: "Chediak-Higashi症候群の責任遺伝子." 医学のあゆみ. 180. 510-511 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "好中球機能発現における細胞内情報伝達機構." 炎症. 17. 231-237 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "先天性遺伝性食細胞機能異常性のmoleculanbasinについての最近の知見" 日臨免誌. 20. 145-151 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "Chediak-Higashi症候群発症遺伝子の同定." 臨床免疫. 29. 1016-1019 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "Chediak-東症候群における責任蛋白質." 医学のあゆみ. 182. 767-770 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三,小宮山敦: "小児の好中球減少症" 日常診療と血液. 7. 1561-1566 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "好中球のシグナル伝達." 炎症と免疫. 6. 63-70 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 片桐麻由美,安井耕三 他: "アスペルギルス肺炎の浸潤により脊髄麻痺をきたした慢性肉芽腸症の1例." 小児内科. 30. 561-566 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 大賀正一,安井耕三他: "顆粒球輸血の考え方-アンケート調査の結果から-." 小児感染免疫. 10. 37-44 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "好中球機能発現と細胞内情報伝達." 小児感染免疫. 10. 105-110 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 清水亜矢子,安井耕三他: "Pentoxifvlineを加えた3剤併用療法が奏功した腸管型Behcet病の小児例" 小児科診療. 61. 1182-1185 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "免疫不全症候群" 小児看護. 21. 1217-1220 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hu B, Yasui K.: "Effects of colony-stimulating factors (CSFS) on neutrophil apoptosis" Int J Hematol. 66. 179-188 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasui K et al.: "Treatment of Behcet disease with pentoxfylline" Ann Intern Med. 126. 493-494 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasui K et al.: "Theophylline accelerates qranulocyte apoptosis not via phosphodiestrasp inhibition" J Clin Invest. 100. 1677-1684 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Higuchi T, et al.: "Megakaryocytes derived from CD34 positive cord blood cells produce interleukin-8" Br J Haematol. 99. 509-516 (1997)

    • Related Report
      1998 Annual Research Report
  • [Publications] Agematsu K et al.: "Generation of plasma cells from peripheral blood memory B cells" Blood. 91. 193-180 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shinozaki K et al.: "Biphasic effects of granulocyte-macrophage" Jpn J Pediacr Hematol. 12. 87-92 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Agematsu K et al.: "Absence of IgD CD27+memory B cell population in" J Clin Invest. 102. 87-92 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsuoka T et al.: "Defective late phase of respiratory burst" Jpn J Obsteric Gynecologic Neonatal Hema. 8. 70-75 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Nagumo H et al.: "CD27/CD70 interaction augments IgE secretion" J Immunol. 161. 6496-6502 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasui K et al.: "Behcet's disease in children" J Pediatr. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasui K et al.: "RhG-CSF therapy for sepsis in infants with" Pesiatrics. inn press.

    • Related Report
      1998 Annual Research Report
  • [Publications] Yasui K et al.: "Presenility of franulocytes in Down syndrome" Am J Med Gener. in press.

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三,小宮山淳: "血液症候群II (別冊日本臨床) 好中球ATP欠損症." 日本臨床社, 91-93 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 安井耕三: "シグナル伝達機構."好中球-機能低下と機能亢進"" 笹田昌孝偏. 医薬ジャーナル, 79-93 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] I.Hu B, Yasui K.: "Effects of colony-stimulating factors (CSFs) on neutrophil apoptosis : possible roles in inflammation site." Int J Hematol. 66. 179-188 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasui K, Ohta K,Komiyama A.: "Treatment of Behcet disease with pentoxifylline." Ann Intern Med. 126. 493-494 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yasui K, Hu B, Nakazawa T, Agematsu K, Komiyama A.: "Theophylline accelerates granulocyte apoptosis not via phosphodiesterase inihibition." J Clin Invest. 100. 1677-1684 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Higuchi T, Koike K, Yasui K, et al.: "Megakaryocytes derived from CD34-positive cord blood cells produce interleukin-8." Br J Haematol. 99. 509-516 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Agematsu K, Nagumo H, Yasui K, et al.: "Generation of plasma cells from peripheral blood memory B cells : Synergistic effect of interleukin-10 and CD27/CD70 interaction." Blood. 91. 173-180 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安井耕三, 小宮山淳: "Chediak-Higash : 症候群の責任遺伝子" 医学のあゆみ. 180. 510-511 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安井耕三: "好中球機能発現における細胞内情報伝達機構." 炎症. 17. 231-237 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安井耕三: "先天性遺伝性食細胞機能異常症のmolecular basisについての最近の知見" 日臨免誌. 20. 145-151 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安井耕三: "Chediak-Higashi症候群発症遺伝子の同定." 臨床免疫. 29. 1016-1019 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安井耕三: "Chediak-東症候群における責任蛋白質." 医学のあゆみ. 182. 767-770 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 安井耕三: "小児の好中球減少症" 日常診療と血液. 7. 1561-1566 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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