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2001 Fiscal Year Final Research Report Summary

Clinical application for pathophysiological analysis, diagnosis and treatment of lung diseases by genes and their products expressed in alveolar type II cells.

Research Project

Project/Area Number 12557057
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Respiratory organ internal medicine
Research InstitutionSapporo Medical University

Principal Investigator

KUROKI Yoshio  Sapporo Medical University School of medicine, Professor, 医学部, 教授 (70161784)

Co-Investigator(Kenkyū-buntansha) MURAKAMI Seiji  Sapporo Medical University School of medicine, Research Associate, 医学部, 助手 (40315487)
IWAKI Daisuke  Sapporo Medical University School of medicine, Research Associate, 医学部, 助手 (10315492)
TAKAHASHI Hiroki  Sapporo Medical University School of medicine, Associate Professor, 医学部, 助教授 (60231396)
NAGAE Hisato  Yamasa Corporation Diagnostic Division, Director, 診断薬部, 主任
Project Period (FY) 2000 – 2001
Keywordsalveolar type II cells / idiopathic interstitial pneumonia / SP-A / SP-D / radiation pneumonitis / autoantibody / Toll-like receptor / lung adenocarcinoma
Research Abstract

The purpose of this study was to pursue clinical application for pathophysiological analysis, diagnosis and treatment of lung diseases by genes and their products expressed in alveolar type II cells. We have identified the antigen to autoantibody existing in sera from patients with idiopathic interstitial pneumonia (IIP), established clinical significance of serum SP-A and SP-D as disease markers and applied lung collectins and pattern recognition receptors for treatment of respiratory infections.
(1) When A549 cell line was examined for immunoreactivity with sera from patients with IIP, approximately 50 % of patient sera reacted positively with A549 cells. Confocal microscopy revealed that the antigen recognized by patient sera localized in the cyoplasm of the cells. Patient IgG immunoprecipitaed 120 kDa protein. Proteome analysis of the 120 kDa protein identified the antigen as alanyl tRNA synthetase. We have cloned DNA for alanyl tRNA synthetase. When we analyzed immunocytochemically … More CHO cells which had been shown to be negative staining for patient IgG and were transfected with CDNA for this enzyme, patient IgG recognized the antigen in CHO cells that colocalized with GFP-labeled alanyl tRNA synthetase. In addition, sera from IIP patients significantly inhibited the enzyme activities of alanyl tRNA synthetase. These results clearly demonstrate that there exists antoantibody to alanyl tRNA synthetase in sera from IIP patients.
(2) Serum SP-A and SP-D increased in patients with radiation pneumonitis. SP-A and SP-D appeared to respond to the small lung damages which was able to detect by CT but not by chest Xp, demonstrating the serological usefulness of SP-A and SP-D as disease markers. In addition, we have establised the detection system of micrometastasis in peripheral blood in patients with lung adenocarcinoma using RT-PCR for SP-A, SP-C and CC10.
(3) We have analyzed the structure-function relationship of Toll-like receptor 2 that has been shown to interact with SP-A and SP-D. and identified the TLR2 region Ser40-Ile64 as the functional region in recognition and signal transduction of Staphylococcal peptidoglycan. Less

  • Research Products

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Saitoh M: "Importance of the carboxy terminal 25 amino acid residues of lung collectins in interactions woth lipids and alveolar type II cells"Biochemistry. 39. 1059-1066 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi H: "Serum levels of surfactant protein A and D are useful markers for interstitial lung disease in natients with progressive systemic sclerosis"Am J Respir Crit care Med. 62. 258-263 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda T: "Purification and characterization of bovine cone arrestin (cArr)"FEBS Lett. 470. 336-340 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi H: "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. 163. 1109-1114 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda A: "Aberrant expression of photoreceptor-specific calcium-binding protein (recoverin) in cancer cell lines"Cancer Res. 60. 1914-1920 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sano H: "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(和文)」より
  • [Publications] Ueda T: "Effects of aging on surfactant forms in rats"Eur Respir J. 15. 80-84 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Bridges JP: "Pulmonary surfactant proteins A and D are potent ihibitors of lipids oxidationand oxidative cellular injury"J Biol Chem. 275. 38848-38855 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Cheng G: "Increased levels of surfactant protein A and D in bronchoalveolar lavage fluids in patients with bronchial asthma"Eur Respir J. 16. 831-835 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takahashi H: "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
  • [Publications] Maeda A: "Identification of human antitumor cytotoxic T.lymphocytes epitope of recoverin, cancer-associated retinopathy antigen, to a clinical better prognosis in a paraneoplastic syndrome"Eur J Immunol. 31. 563-572 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Maeda T: "Mechanisms of phtoreceptor cell death in cancer-associated retinopathy ; effects of anti-recoverin antibody on rhodopsin phosphorylation and roles of abberant"Invest Ophth Vis Sci. 42. 705-712 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Chiba H: "Rat mannose-binding protein A binds CD14"Infect Immun. 69. 1587-1592 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sohma H: "Differential lipid specificites of repated domains of annexin IV"Biochim Biophys Acta. 1546. 205-215 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sohma H: "Binding of annexins to lung lamellar bodies and the PMS-stimulated secretion of annexin V from alveolar type II cells"J Biochem. 130. 449-455 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Mistuzawa H: "Extracellular Toll-like receptor 2 region containing Ser4O-Ile64 but not Cys3O-Ser39 is critical for the reco gnition of Staphylococcus aureus peptidoglycan"J Biol Chem. 276. 41350-41356 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Murakami S: "Surfactant protein A inhibits peptidoglycan-induced TNF-a secretion in U937 cells and alveolar macrophages by direct interaction with Toll-like receptor 2"J Biol Chem. 277. 6830-6837 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩城大輔: "サーファクタント関連遺伝子"THE LUNG Perspectives. 8. 304-310 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野仁美: "気道免疫防御におけるSP-Aの役割"気管支. 22. 650-656 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 高橋 亨: "GM-CSFノックアウトマウス"分子呼吸器病学. 5. 45-51 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 千葉弘文: "肺サーファクタント蛋白の構造と機能:phage display peptide libraryを用いた解析"分子呼吸器病. 6. 19-21 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 黒木由夫: "Surfactantの生化学"THE LUNG Perspectives. 9. 392-401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 黒木由夫: "基礎生化学実験法講座 第5巻 第1部 第6章 サーファクタント"同人化学社. 338 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 岩城大輔: "エンドトキシン研究3 CD14との相互作用を介する肺サーファクタント蛋白質によるLPS誘導細胞応答の制御"菜根出版. 218 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 黒木由夫: "Annual review 免疫2001:CD14を介するサーファクタント蛋白質によるLPS誘導細胞応答制御"中外医学社. 372 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 佐野仁美: "呼吸器疾患-診断と治療の最前線-第1章 3.気道免疫防御機構と肺サーファクタント蛋白質"先端医療技術研究所. 489 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Saitoh M.: "Importance of the carboxy terminal 25 amino acid residues of lungcollectins in interactions with lipids and alveolar type II cells"Biochemistry. 39. 1059-1066 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi H.: "Serum levels of surfactant proteins A and D are useful markers for interstitial lung disease in patients with progressive systemic sclerosis."Am J Respir Crit Care Med. 62. 258-263 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda T.: "Purification and characterization of bovine cone arrestin."FEBS Left. 470. 336-340 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi H.: "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.. 163. 1109-1114 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Maeda A.: "Aberrant expression of photoreceptor-specific calcium-binding proteim (recoverin) in cancer cells"Cancer Res.. 60. 1914-1920 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sano H.: "Suifactant 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
  • [Publications] Ueda T.: "Effects of aging on surfactant forms in rats"Eur. Respir J.. 15. 80-84 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Bridges JP.: "Pulmonaru surfactant proteins A and D are potent inhibitors of lipids oxidation and oxidative cellular injury."J Biol Chem.. 275. 38848-38855 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Cheng G.: "Increased levels of surfactant proteins A and D in bronchoalveolar lavage fluids in patients with bronchial asthma."Eur. Respir J.. 16. 831-835 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takahashi H.: "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(欧文)」より
  • [Publications] Maeda A.: "Identification of human antitumor cytotoxic T lymphocytes epitope ot recoverin, cancer-associated retinopathy antigen, to achieve a clinical better prognosis in a.paraneoplastic syndrome"Eur. J Immunol.. 31. 563-572 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Chiba H.: "rat mannose-binding protein A binds CD14"Infect Immun.. 69. 1587-1592 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sohma H.: "Differential lipid specificities of repeated domains of annexin IV"Biochim. Biophy.s Acta. 1546. 205-215 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sohma H.: "binding of annexins to lung lamellar bodies and the PMA-stimulated secretion of annexin V from alveolar type II cells".J Biochm.. 130. 449-455 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Mitsuzawa H.: "Extracellular Toll-like receptor 2 region containing Ser40-Ile64 but not Cys30-Ser39 is critical for the recognition of Staphylococcus aur bus peptidoglycan"J. Biol. Chem.. 276. 6830-6837 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Murakami S.: "Surfactant protein A inhibits peptidoglycaii-induced TNF-alpha secretion in U937 cells and alveolar macrophages by direct interaction with Toll-like receptor 2"J. Biol. Chem.. 277. 6830-6837 (2002)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2003-09-17  

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