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Determination of surfactant proteins SP-A and SP-D in serum and its clinical application to lung diseases

Research Project

Project/Area Number 05557035
Research Category

Grant-in-Aid for Developmental Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Respiratory organ internal medicine
Research InstitutionSapporo Medical University

Principal Investigator

AKINO Toyoaki  Sapporo Medical University School of Medicine Department of Biochemistry Professor, 医学部, 教授 (80045377)

Co-Investigator(Kenkyū-buntansha) NAGATA Atsuo  Yamasa Co., Section of Diagnostics Research Head, 診断部・免疫研究室, 室長 (00129157)
HOSODA Kenji  Teijin Co., Institute of Bio-Medicine, Research Associate, 医療診断研究所, 主任研究員
HONDA Yasuhito  Sapporo Medical University School of Medicine Dept. Internal medicine Assistant, 医学部, 講師 (70190270)
ABE Shyosaku  Sapporo Medical University School of Medicine Dept. Internal medicine professor, 医学部, 教授 (60113510)
KUROKI Yoshio  Sapporo Medical University School of Medicine Department of Biochemistry Associa, 医学部, 助教授 (70161784)
相馬 仁  札幌医科大学, 医学部, 講師 (70226702)
Project Period (FY) 1993 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥7,300,000 (Direct Cost: ¥7,300,000)
Fiscal Year 1994: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1993: ¥4,600,000 (Direct Cost: ¥4,600,000)
KeywordsPulmonary surfactant / Surfctant apoproteins / Serum assay method / Idiopathic interstitial pneumonitis / Diffuse lung disease / SP-A / SP-D / Immunoglobulin / ぴまん性肺疾患
Research Abstract

Lung surfactant contains four specific proteins, i.e., SP-A,SP-B,SP-C and SP-D.In this study, we planed to establish the determination method of SP-A or SP-D using monoclonal antibodies, and to clarify the clinical significance of SP-A or SP-D appearance into the bloodstream.
1. We established the high sensitive ELISA of SP-A assay ; assay kit for its practical use. The cut-off value of serum SP-A concentration was 43,8 ng /ml. The positive percentage in idiopathic interstitial pneumonitis (IIP) and pulmonary alveolar proteinosis (PAP) was more than 50%. Therefore, the determination of serum SP-A could provide a useful tool as a serum marker for IIP and PAP.
2. We established the ELISA of SP-D ; assay kit for practical use (the liscence is being applied). The cut-off value of serum SP-D was 136 ng/ml. The positive percentage in IIP and PAP was 92% and 88%, respectively. In contrast, SP-D levels in bronchoalveolar lavage fluids were significantly low in IIP,but predoninantly high in PAP,suggesting that the mechanism of SP=A appearance into the bloodstream may be different between in IIP and PAP.
3. SP-A isolated from the alveoli of PAP patients was found to have an abnormal change in oligomeric structure. This abnormal SP-A had abnormal functions, i.e., binding to nonimmune IgG and disfunction in forming tubular myelin structure.

Report

(3 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • Research Products

    (71 results)

All Other

All Publications (71 results)

  • [Publications] Kuroki,Y.: "Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis." American Review of Respiratory Medicine. 147. 723-729 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsuzuki,A.: "Pulmonary surfactnt protein A-mediated uptake of phosphatidylcholine by alveolar type II cells." American Journal of Physiology. 265. L193-L199 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Murata,Y.: "Role of the carboxyl terminal domain of pulmonary surfactant protein A in binding to alveolar type II cells." Biochemical Journal(U.K.). 291. 71-76 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda,Y.: "Surfactant protein A (SP-A) concentration in bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis." Chest. 103. 496-499 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsutahara,S.: "Lung adenocarcinoma with type II pneumocyte characteristics." European Respiratory Journal. 6. 135-137 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 秋野豊明: "肺サーファクタントの生化学-アポ蛋白質をめぐる展開-" 日本胸部疾患誌. 30. 5-14 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 黒木由夫: "ARDSと肺サーファクタント" The Lung. 2. 63-67 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 黒木由夫: "C型レクチンに属する肺サーファクタント・アポ蛋白質の脂質結合性" 生化学. 66. 53-57 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 秋野豊明: "びまん性肺疾患と肺サーファクタントの変動" 医学のあゆみ. 167. 670-674 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Inoue,T.: "Enzyme-linked Immunosorbent assay for human pulmonary surfactant protein D." Jounal of Immunological method. 173. 157-164 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kuroki,Y.: "Pulmonary surfactant proteins" Journal of Biological Chemistry. 269. 25943-25946 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 秋野豊明: "サーファクタントの生化学と今後の臨床展望" 日本未熟児新生児誌. 6. 13-22 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 小笠原由法: "肺サーファクタント蛋白質の構造と機能" The Lipids. 5. 440-447 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 渡部智之: "病態肺における肺サーファクタントの変動に関する研究 第1報 N-nitroso-N-methylurethane投与により惹起される急性肺障害-ARDSモデル-" 札幌医学誌. 63. 149-159 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 渡部智之: "病態肺における肺サーファクタントの変動に関する研究 第2報 気道内silica投与により惹起される慢性肺障害-肺胞蛋白症モデル-" 札幌医学誌. 63. 161-167 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Hiraike,N.: "Epitope mapping for monoclonal antibody against human surfactant protein A (SP-A) alters receptor binding of SP-A and the SP-A dependent regulation of phospholipid secretion by alveolar type II cells." Biochimica et Biophysica Acta. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda,Y.: "Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic fibrosis and its clinical significance." Respiration. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shijubo,K.: "Lung surfactant protein A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma." European Respiratory Journal. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda,Y.: "Determination of surfactant protein A in sera and bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis." European Respiratory Journal. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi,H.: "Pulmonary Surfactant protein A:a serum marker of pulmonary fibrosis in patients with collagen vascular diseases." Clinica Chimica Acta. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda,Y.: "Pulmonary surfactant protein D in sera and bronchoalveolar fluids." American Journal of Respiratory and Critical Care Medicine. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 秋野豊明: "サーファクタントの生化学と展望" 日本界面医学誌. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 阿部庄作: "各種肺疾患における血清肺サーファクタント蛋白質-Aの臨床的意義-" 日本胸部疾患誌. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kari,M.: "Prenatal dexamethasone and exogenous surfactant therapy surfactant indices in airway specimens." American Journal 0f Respiratory and Critical Care Medicine. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Robertson,B.: "Alveolar-to-vascular leakage of surfactant protein A in ventilated immature newborn rabbits." Biological Neonate. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Veldhuizen,R.A.W.: "Pulmanary surfactant subfractions in patients with the acute respiratory distress syndrome(ARDS)" American Journal Respiratory and Critical Care Medicine. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akino, T.: "Biochemistry of pulmonary surfactant-New aspects of surfactant apoproteins." Jpn.J.Thorac.Dis.30. 5-14 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kuroki, Y.: "Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar proteinosis." Am.Rev.Respir.Dis.147. 723-729 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kuroki, Y.: "Lipid binding specificities of pulmonary surfactant apoproteins having C-type lectin structure." SEIKAGAKU. 66. 53-57 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Murata, Y.: "Roles of the carboxyl terminal domain of pulmonary surfactant protein A in binding to alveolar type II cells and requlation of phospholipid secretion." Biochem.J.291. 71-76 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Tsuzuki, A.: "Pulmonary surfactant protein A-mediated uptake of phosphatidylcholine by alveolar type II cells." Am.J.Physiol.265. L193-L199 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akino, T.: "Biochemistry of pulmonary surfactant and its future aspects in clinical application." J.Jpn.Soc.Premat.Newborn Med.6. 13-22 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Inoue, T.: "Enzyme-linked immunosorbent assay for human pulmonary surfactant protein D." J.Immun.Meth.173. 157-164 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Kuroki, Y.: "Pulmonary surfactant proteins." J.Biol.Chem.269. 25943-25946 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Ogasawara, Y.: "Structure and function of lung surfactant proteins." The lipids. 5. 440-447 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Watanabe, T.: "Studies on changes in pulmonary surfactant in pathological states of the lung.1.Acute lung injury induced by N-nitro-N-methylurethane : ARDS model." Sapporo Med.J.63. 149-159 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda, Y.: "Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic fibrosis and its clinical significance." Respiration. in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Shijubo, K.: "Lung surfactant protein A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma." Eur.Respir.J.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda, Y.: "Determination of surfactant protein A in sera and bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis." Eur.Respir.J.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Takahashi, H.: "Pulmonary surfactant protein A. : a serum marker of pulmonary fibrosis with collagen vascular diseases." Clin.Chim.Acta. in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Honda, Y.: "Pulmonary surfactant protein D in sera and bronchoalveolar fluids." Am.J.Respir.Crit, Care Med.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Abe, S.: "Clinical significance of serum surfactant protein A levels in various lung diseases." Jpn.J.Thorac.Dis.in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Akino, T.: "Biochemistry and new aspects of lung surfactant." J.Jpn.med.Soc.Biol.Interface. in press. (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Inoue,T.: "Enzyme-linked immunosorbent assay for human pulmonary surfactant D." J.Immunol.Method. 173. 157-164 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kuroki.Y.: "Pulmonary surfactant proteins" J.Biol.Chem.269. 25943-25946 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiraike,N.: "Eoitope mapping for monoclonal antibody against human surtactart protein A(SP-A)alters receptor binding of SP-A and the SP-A dependent regulation of phospbo lipid ecret on by alveolar type II cells." Biochim.Biophys.Acta. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 秋野 豊明: "サーファクタントの生化学と今後の臨床展望" 日本未熟児新生児誌. 6. 13-22 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 小笠原由法: "肺サーファクタント蛋白質の構造と機能" The Lipids. 5. 440-447 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 渡辺 智之: "病態肺における肺サーファクタントの変動に関する研究 第1報 N-nitroso-N-methylurethane投与により惹起される急性肺障害-ARDSモデル-" 札幌医学雑誌. 63. 149-159 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 渡辺 智之: "病態肺における肺サーファクタントの変動に関する研究 第2報 気道内silica投与により惹起される慢性肺障害-肺胞蛋白症類似モデル-" 札幌医学雑誌. 63. 161-167 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,Y.: "Aberrant appearance of lung surfactant protein A in sera of patients with idiopathic fibrosis and its clinical significance." Respiration. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shijubo,K.: "Lung surfactant protein A and carcinoembryonic antigen in pleural effusions due to lung adenocarcinoma and malignant mesothelioma" Eur.Respir.J.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,Y.: "Determination of surfactant protein A in sera and bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis." Eur.Respir.J.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Takahashi,H.: "Pulmonary surfactant protein A: a serum marker of pulmonary fibrosis in patients with collagen vascular diseases." Clin.Chim.Acta. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Honda,Y.: "Pulmonary surfactant protein D in sera and bronchoalveolar fluids" Am.J.Respir.Crit.Care Med.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 秋野 豊明: "サーファクタントの生化学と展望" 日本界面医学誌. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 阿部 庄作: "各種肺疾患における血清肺サーファクタント蛋白質-Aの臨床的意義" 日本胸部疾患誌. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kari,M.: "Prenatal dexamethasone and exogenous surfactant therapy-surfactant indices in airway specimens." Am.J.Respir.Crit.Care Med.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Robertson,B.: "Alveolar-to-vascular leakage of surfactant protein A in ventilated immature newborn rabbits." Biol.Neonate. (in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Veldhuizen,R.A.W.: "Pulmonary surfactant subfractions in patients with the acute respiratory distress syndrome(ARDS)." Am.J.Respir.Crit.Care Med.(in press). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kuroki,Y.: "Elevated levels of lung surfactant protein A in sera from patients with idiopathic pulmonary fibrosis and pulmonary alveolar protei-nosis" American Review of Respiratory Medicine. 147. 723-729 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsuzuki,A.: "Pulmonary surfactant protein A-mediated uptake of phosphatidyl-choline by alveolar type II cells" American Journal of Physiology. 265. L193-L199 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Murata,Y.: "Role of the carboxyl terminal domain of pulmonary surfactant protein A in binding to alveolar type II cells." Biochemical Journal(U.K.). 291. 71-76 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Honda,Y.: "Surfactant protein A(SP-A)concentration in bronchoalveolar lavage fluids of patients with pulmonary alveolar proteinosis." Chest. 103. 4 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Tsutahara,S.: "Lung adenocarcinoma with type II pneumocyte characteristics." European Respiratory Journal. 6. 135-137 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 秋野豊明: "肺サーファクタントの生化学-アポ蛋白質をめぐる展開-" 日本胸部疾患誌. 30. 5-14 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 黒木由夫: "ARDSと肺サーファクタント" The Lung. 2. 63-67 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 黒木由夫: "C型レクチンに属する肺サーファクタント・アポ蛋白質の脂質結合特異性" 生化学. 66. 53-57 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 秋野豊明: "びまん性肺疾患と肺サーファクタントの変動" 医学のあゆみ. 167. 670-674 (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] Inoue,T.: "Enzyme-linked immunosorbent assay for human pulmonary surfactant protein D." Journal Immunological Method in press. (1994)

    • Related Report
      1993 Annual Research Report
  • [Publications] 秋野豊明: "サーファクタントの生化学と今後の臨床展望" 日本未熟児新生児誌. 6. (1994)

    • Related Report
      1993 Annual Research Report

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Published: 1993-04-01   Modified: 2016-04-21  

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