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Type II pneumocytes as a protective factor against interstitial lung injury

Research Project

Project/Area Number 13670609
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 School of Medicine

Principal Investigator

TAKAHASHI Hiroki  Sapporo Medical University School of Med Associate Prof, 医学部, 助教授 (60231396)

Co-Investigator(Kenkyū-buntansha) SHIRATORI Masanori  Sapporo Medical University School of Med Instructor, 医学部, 助手 (40295366)
KUORKI Yoshio  Sapporo Medical University School of Med Professor, 医学部, 教授 (70161784)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2001: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywordsangiotensin receptor 1 / Candesartan / interstitial lung injury / lung fibrosis / type II pneumocytes / alveolar macrophage / neutrophil / 肺線維化 / Renin-Angiotensin系 / Angiotensin II receptor 1 / candesartan / 肺胞II型上皮細胞 / 急性肺傷害 / 線維化 / アンギオテンシンII / ブレオマイシン
Research Abstract

Interstitial lung diseases involve a group showing poor prognosis including idiopathic pulmonary fibrosis (IPF). A common pathophysiological change is irreversible fibrosis.
In lung tissues injured in alveolar interstitum, to make alveolar epithelial cells regenerate is very important for repair of the injured lung. Several recent studies showed that rennin-angiotensin system induces lung fibrosis and that apoptosis of type II pneumocytes is a key factor of its mechanism. However, precise manner of this system is unknown. Aims of this study were to clarify a mechanism of interstital lung injury and following fibrosis via angiotensin II receptor 1 (AT1) and to estimate an efficacy of AT1 selective antagonist (Candesartan) as a therapeutic agent against bleomycin-induced lung injury prepared in rats. Distribution of expression of AT1 receptors in normal lungs was nonspecific for many types of cells including alveolar macrophages and type II pneumocytes. Their expression in injured lungs was more extensive in neutrophils, alveolar macrophages and fibroblasts than in other types of cells. Administration of Candesartan significantly inhibited an increased content of hydroxyproline as a quantitative indicator of fibrosis, and an increased cell number of neutrophils and alveolar macrophages, whereas it did not inhibit an increased expression of AT1. Thus, this AT1 antagonist may provide an ability to modulate a process of fibrosis in the lung. A speculated mechanism by the AT1 antagonist is based on prevention of apoptosis of type II pneumocytes.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Takahashi H, et al.: "Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis"Eur Respir J.. 17. 481-487 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba H., Takahashi H, et al.: "Rat mannose-binding protein A binds CD 14"Infect Immun. 69. 1587-1592 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Abe S, Takahashi H: "Difufse infiltrative lung disease : New clinical biomarker in diffuse interstitial pneumonia"Internal Med.. 40. 159-162 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami S, Takahashi H, et al.: "Surfactant Protein A (SP-A) inhibits Peptidoglycan-induced cellular responses"Proc Airway Secret Res. 4. 37-44 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takezawa C, Takahashi H, et al.: "Assessment of differentiation in adenocarcinoma cells from pleural effusion by peripheral airway cell markers and their diagnostic values"Lung Cancer. 38. 273-281 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami S, Takahashi H, et al.: "Surfactant protein A inhibits peptidoglycan-induced tumor necrosis factor-a secretion in U937 cells and alveolar macrophages by direct interaction with toll-like recptor 2"J Biol Chem. 277. 6830-6837 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis"Eur Respir J. 17(3). 481-487 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chiba H., Takahashi T., et al.: "Rat mannose-binding protein A binds CD14"Infect Immun. 69(3). 1587-1592 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Abe S., Takahashi H.: "Difufse infiltrative lung disease : New clinical biomarker in diffuse interstitial pneumonia"Internal Med. 40. 159-162 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami S, Takahashi H, et al.: "Surfactant Protein A (SP-A) inhibits Peptidoglycan-induced cellular responses"Proc Airway Secret Res. 4. 37-44 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takezawa C, Takahashi H, et al.: "Assessment of differentiation in adenocarcinoma cells from pleural effusion by peripheral airway cell markers and their diagnostic values"Lung Cancer. 38(3). 273-281 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Murakami S, Takahashi H, et al.: "Surfactant protein A inhibits peptidoglycan-induced tumor necrosis factor-a secretion in U937 cells and a lveolar macrophages by direct interaction with toll-like recptor 2"J Biol Chem. 277(9). 6830-6837 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi H, et al.: "Diagnostic significance of surfactant proteins A and D in sera from patients with radiation pneumonitis"Eur Respir J.. 17・3. 481-487 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Chiba H., Takahashi H, et al.: "Rat mannose-binding protein A binds CD 14"Infect Immun. 69・3. 1587-1592 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Abe S, Takahashi H.: "Difufse infiltrative lung disease : New clinical biomarker in diffuse interstitial pneumonia"Internal Med.. 40・2. 159-162 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murakami S, Takahashi H, et al.: "Surfactant Protein A (SP-A) inhibits Peptidoglycan-induced cellular responses"Proc Airway Secret Res. 4・1. 37-44 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takezawa C, Takahashi H, et al.: "Assessment of differentiation in adenocarcinoma cells from pleural effusion by peripheral airway cell markers and their diagnostic values"Lung Cancer. 38・3. 273-281 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murakami S, Takahashi H, et al.: "Surfactant protein A inhibits peptidoglycan-induced tumor necrosis factor-a secretion in U937 cells and alveolar macrophages by direct interaction with toll-like recptor 2"J Biol Chem. 277・9. 6830-6837 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Takahashi H: "Diagnostic significance of surfactant protein A and D in sera from patients with radiation pneumonitis"Eur Respir J. 17. 481-487 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Murakami S: "Surfactant protein A inhibits poptidoglycan-induced TNF-alpha secretionin U937 cells and alveolar macrophages by direct interaction with toll-like receptor ?"J. Biol. Chem. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Chiba H: "Rat wannose-binding protein A binds CD14"Infect Immun. 69. 1587-1592 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋弘毅: "間質性肺傷害微小変化の血清マーカーとしてのSP-A, SP-D"日本界面医学会誌. 32. 11-16 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Abe S: "Difufse infiltrative lung disease : New clinical biomarker in diffuse interstitial pneumonia"Int. Med.. 40. 159-162 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 高橋弘毅: "呼吸器疾患理解のための基礎分子医学:呼吸器疾患と肺サーファクタント蛋白質"日本胸部臨床. 60. S206-S212 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] 白鳥正典: "間質性肺炎・急性肺傷害における肺胞II型上皮細胞の役割"気管支学. 23・8. 721-725 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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