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MOLECULAR BIOLOGICAL STUDY FOR EFFECT OF PULMONARY SURFACTANT PROTEINS ON HOST DEFENSE MECHANISM IN LUNG

Research Project

Project/Area Number 11670585
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionSAPPORO MEDICAL UNIVERSITY

Principal Investigator

TAKAHASHI Hiroki  SCHOOL OF MEDICINE, SAPPORO MEDICAL UNIVERSITY, ASSOCIATE PROFESSOR, 医学部, 助教授 (60231396)

Co-Investigator(Kenkyū-buntansha) KUROKI Yoshio  SCHOOL OF MEDICINE, SAPPORO MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (70161784)
ABE Shosaku  SCHOOL OF MEDICINE, SAPPORO MEDICAL UNIVERSITY, PROFESSOR, 医学部, 教授 (60113510)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 2000: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsPULMONARY SURFACTANT / SP-A / SP-D / IDIOPATHIC PULMONARY FIBROSIS / ALVEOLAR MACROPHAGE / CD14
Research Abstract

Idiopathic pulmonary fibrosis (IPF) are often exacerbated by a trigger of respiratory infection which is the highest risk factor to threaten patients with death. We had reported that concentrations of serum surfactant protein (SP)-A and -D, collectins derived from lung, show to be low in alveolar washing fluids from patients with IPF, while high in sera from the patients when compared to healthy adults. Considering based on these results, we proposed a hypothesis that alteration in concentration of the intrapulmonary and serum collectins affects progress of IPF and prognosis.
Investigation of outcome in patients with IPF in a 3-year-observation period revealed that concentrations of serum collectins at an initial time-point of observation were significantly higher in nonsurvivors than in survivors. Experiments using an animal model of interstitial lung injury showed that concentrations of collectins decreased in lung and increased in blood, and that an leakage of the collectins from lung to bloodstream was caused by the damage of basement membrane in alveolar wall. In in vitro experiments, it was clarified SP-A possesses abilities to bind with LPS and CD14, and to modulate the cellular response by LPS on U937 cells. SP-A also inhibited TNF-∂ release stimulated by peptidoglycan (PGN), derived from Staphylococcus aureus, in alveolar macrophages and U937 cells.
The results are consistent with our hypothesis that pulmonary collectins prevent progress of inflammation and that the abnormal decrease in concentrations of intrapulmonary collections may lead to acute exacerbation of IPF.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Takahashi H, et al.: "Serum Levels of Surfactant Proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis."Am J Respir Crit Care Med. 162(1). 258-263 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosi and their relationship to disease extent."Am J Respir Crit Care Med. 162(3). 1109-1114 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Serum surfactant protein A and D in idiopathic pulmonary fibrosis ; Relationship with disease extent and prognosis."Applied Cardiopulmonary Pathophysiology. 9(3). 304-305 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Diagnostic significance of surfactant protein A and D in sera from patients with radiatio pneumonitis."Eur Respir J. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba H, et al: "Rat mannose-binding protein A binds CD14."Infect Immun. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 阿部庄作,高橋弘毅: "呼吸器疾患の分子病態と臨床-びまん性肺疾患."日本内科学会雑誌. 89. 1804-1808 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 高橋弘毅,阿部庄作: "標準呼吸器病学;呼吸器の防御機構"泉孝英 編集,標準呼吸器病学,医学書院,東京,2000,53-69.. 462 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Diagnostic significance of surfactant protein A and D in sera from patients with radiation pneumonitis."Eur Respir J. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba H, et al.: "Rat mannose-binding protein A binds CD14."Infect Immun. 69. 1587-92 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Serum Levels of Surfactant Proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis."Am J Respir Crit Care Med. 162. 258-263 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosis and their relationship to disease extent."Am J Respir Crit Care Med. 162. 1109-14 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Serum surfactant protein A and D in idiopathic pulmonary fibrosis ; Relationship with disease extent and prognosis."Applied Cardiopulmonary Pathophysiology. 9. 304-305 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Abe S, et al.: "Difufse infiltrative lung disease : New clinical biomarker in diffuse interstitial pneumonia."Int.Med.. 40. 159-162 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sano H, et al.: "Surfactant proteins A and D bind CD14 by different mechanisms."J Biol Chem. 275. 22442-22451 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murakami M, et al.: "The mechanisms by which surfactant protein A and D appear in the bloodstream and the intra-alveolar space are different between idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis."Airway Secetion Res. 2. 57-64 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sano H, et al.: "Pulmonary surfactant protein A modulates the cellular responses to smooth and rough lipopolysaccharides by interaction with CD14."J Immunol. 163. 387-395 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chiba H, et al.: "Introduction of mannose binding protein-type phosphatidylinositol recognition into pulmonary surfactant protein A."Biochemistry. 38. 7321-7333 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Serum Levels of Surfactant Proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis."Am J Respir Crit Care Med. 162(1). 258-263 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi H, et al: "Serum surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibrosi and their relationship to disease extent."Am J Respir Grit Care Med. 162(3). 1109-1114 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi H, et al.: "Serum surfactant protein A and D in idiopathic pulmonary fibrosis ; Relationship with disease extent and prognosis."Applied Cardiopulmonary Pathophysiology. 9(3). 304-305 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Takahashi H. et al.: "Diagnostic significance of surfactant protein A and D in sera from patients with radiatio pneumonitis."Eur Respir J. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Chiba H, et al: "Rat mannose-binding protein A binds CD14."Infect Immun. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] 阿部庄作,高橋弘毅: "呼吸器疾患の分子病態と臨床-びまん性肺疾患."日本内科学会雑誌. 89. 1804-1808. (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 高橋弘毅,阿部庄作: "標準呼吸器病学;呼吸器の防御機構"泉孝英 編集,標準呼吸器病学,医学書院,東京,2000,53-69.. 462 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] H. Takahashi: "serum levels of surfactant proteins A and D are useful biomarkers for interstitial lung disease in patients with progressive systemic sclerosis"Am. Rev. Crit. Care Med.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] H. Takahashi: "serum levels of surfactant proteins A and D as prognostic factors in idiopathic pulmonary fibiosis and their relationship to desease extent"Am. Rev. Crit. Care Med.. (in press).

    • Related Report
      1999 Annual Research Report
  • [Publications] 今井 良成: "放射線肺炎発症過程に伴う肺サーファクタント蛋白質A代謝の変調とその診断的意義"札幌医誌. 68. 1-12 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 近藤 有好: "肺結核における血清サーファクタントプロテイン-D(SP-D)の意義"結核. 73. 585-590 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 高橋 弘毅: "肺線維化:肺サーファクタントと線維化"THE LUNG prospective. 7. 25-30 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 黒木 由夫: "肺サーファクタント蛋白質SP-AおよびSP-D"日本臨床. 57. 309-312 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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