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Basic Study on Lung Injuries and Neutrophils-Isolation and Purification of Alveolus-Derived Neutrophil Inhibitory Factor and Its Effects on The Development of Lung Injuries-

Research Project

Project/Area Number 08670650
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SUWABE Akira  YAMAGATA UNIV., DEPT.OF MED., RESEARCH ASSIST, 医学部, 助手 (20241713)

Co-Investigator(Kenkyū-buntansha) TAKAHASHI Keiji  KANAZAWA MED.SCH,DEPT OF MED., PROFESSOR, 医学部・呼吸器内科, 教授 (50004685)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
KeywordsLUNG INJURY / NEUTROPHILS / SUPEROXIDES / SURFACTANT
Research Abstract

In the development of lung injury, the infiltrating neutrophils and their injury-causative agents, such as protease or active oxygen radicals are mainly involved. Most of the therapies have not been effective for those disease states and the prognosis of these patients are still poor.
We have focused on the neutrophil inhibitory factors found in the pulmonary alveolus. In a series of these studies, we reported that rat lung surfactant and rat alveolar type II cells directory inhibited human neutrophil superoxide production. We also found another neutrophil inhibitory factors in the soluble fraction of the bronchoalveolar lavage fluids in rats. These inhibitory activities were destroyed by treating the samples at 100゚C for 10min, suggesting that inhibition was derived from the protein components. The inhibitory factors were also shown to be different from those previously described, such as superoxide disumutase (SOD) and were expected to be new therapeutic agents for the patients with l … More ung injuries.
In the researches in 1996, we have shown that the inhibitory effect was independent of that by surfactant specific proteins, such as SP-A or SP-D.
In the next year, we focused on one of the inhibitory cytokines, transforming growth factor-beta (TGF-beta) as the candidate of neutrophil inhibitory factors. We tried the experiments (1) showing whether human TGF-beta can inhibit human neutrophil functions, (2) measuring the TGF-beta concentration in the lung lavage fluids, and (3) neutralizing the inhibitory activities by anti-TGF-beta antibodies. The results, however, were not satisfactory by the reasons of the species difference between human and rats, the high nonspecific adsorbent activity of this cytokine. Although we determined the approximate molecular weight of these inhibitory activities around 200-300 kDa, we were unable to purify these inhibitory proteins since inhibitory activities were lost during the purification procedures. The goal of the present study has not been achieved at this point, but we further need to purify these inhibitory molecules and to establish the specific monoclonal antibody recognizing these molecules. Less

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 諏訪部 章: "ARDSとサーファクタント" 呼吸と循環. 46. 555-561 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 諏訪部 章, 伊藤 未幸, 富永 真琴: "難治性呼吸器疾患のサーファクタント特異蛋白に関する研究ーサーファクタント・プロテイン-Aの構造および機能異常" (財)小野医学研究財団第8回研究成果報告書. 8. 167-175 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 諏訪部 章: "肺サーファクタントと生体防御" 肺サーファクタント基礎講座. 11月号. 1-8 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 伊藤 未幸, 諏訪部 章, 鈴木 優紀, 富永 真琴, 高橋 敬治: "人工サーファクタントのブレオマイシン傷害肺およびラット肺線維芽細胞増殖に及ぼす効果" 日本胸部疾患学会誌. 35. 1163-1172 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 諏訪部 章, 伊藤 未幸, 富永 真琴, 高橋 敬治: "サーファクタント-TAのラット肺胞II型細胞のサーファクタント代謝に及ぼす効果" J.Jpn.Med.Soc.Biol.Interface. 28. 66-69 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] A Suwabe, RJ Mason, DR Voelker: "Calcium dependent association of surfactant protein A with pulmonary surfactant:Application to simple surfactant protein A purification" Arc Biochem Biophys. 327. 285-291 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akira Suwabe: "ARDS and lung surfactant." Kokyu-to-Junkan. 46. 555-561 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akira Suwabe, Miyuki Ito, Makoto Tominaga: "Studies on surfactant specific proteiss in diffuse pulomonary disease." The Eighth Report of Ono Research Fundation. 8. 167-175 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Akira Suwabe: "Lung surfactant and the lung defense." Basic Lecture on Lung Surfactant. 11. 1-8 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyuki Ito, Akira Suwabe, Toshiki Suzuki, Makoto Tominaga, Keiji Takahashi: "The effects of surfactant-TA on bleomycin-induced lung injury and the proliferation of rat pulmonary fibroblasts." J.of Jpn.Thoracic Disease. 35. 1163-1172 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Miyuki Ito, Akira Suwabe, Makoto Tominaga, Keiji Takahashi: "The Effects of surfactant-TA on the surfactant metabolisms by rat alveolar type II cells." J.Jpn.Med. Soc.Biol.Interface. 28. 66-69 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Suwabe, A., Mason, R.J., and Voelker, D.R.: "Calcium dependent association of surfactant protein A with pulmonary surfactant : application to simple surfactant protein A purification" Arch.Biochem.Biophys.327. 285-291 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 諏訪部 章: "ARDSとサーファクタント" 呼吸と循環. 46. 555-561 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 諏訪部章、 伊藤未幸、 富永真琴: "難治性呼吸器疾患のサーファクタント特異蛋白に関する研究ーサーファクタント・プロティン-Aの構造および機能異常" (財)小野医学研究財団第8回研究成果報告書. 8. 167-175 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 諏訪部 章: "肺サーファクタントと生体防御" 肺サーファクタント基礎講座. 11月号. 1-8 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 伊藤未幸、 諏訪部章、 鈴木倪紀、 富永真琴、 高橋敬治: "人工サーファクタントのブレオマイシン傷害肺およびラット肺線維芽細胞増殖に及ぼす効果" 日本胸部疾患学会誌. 35. 1163-1172 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 諏訪部章、 伊藤未幸、 富永真琴、 高橋敬治: "サーファクタント-TAのラット肺胞II型細胞のサーファクタント代謝に及ぼす効果" J. Jpn. Med. Soc. Biol. Interface. 28. 66-69 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Suwabe.A,Mason.R.J.,Voelker.D.R: "Calcium dependent association of surfactant protein A with pulmonary surfactant : application to simple surfactant protein A purification." Arch. Biochem. Biophys.327. 285-291 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] "Protective roles of lung surfactant on neutrophilmediated lung injury." J Jpn. Med Soc Biol Interface. 26(Suppl). 67-88 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 諏訪部章、大竹和久、八鍬直、鈴木博貴、高橋敬治: "サーファクタント・TAのヒト末梢血好中球の接着能および形態に及ぼす影響" 日本胸部疾患学会誌. 34. 290-295 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 諏訪部章: "肺胞II型上皮細胞の新しい機能-肺傷害に対する防御と肺胞免疫調節" 医学のあゆみ. 178. 128-129 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 諏訪部章、伊藤未幸、高橋敬治: "エリスロマイシンのラット肺胞II型上皮細胞のサーファクタント代謝に及ぼす効果" 日本胸部疾患学会誌. 34. 1104-1108 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 諏訪部章、板坂美代子、鈴木博貴、伊藤未幸、高橋敬治: "ラット肺胞II型上皮細胞の好中球スーパーオキサイド産生に対する抑制効果" 日本胸部疾患学会誌. 34. 1208-1215 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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