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Molecular analysis of MPO for patient with autoimmune disease ANCA

Research Project

Project/Area Number 05670212
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionNational Institute of Health

Principal Investigator

SUZUKI Kazuo  National Institute of Health, Bioactive Mol., Lab Chief., 生物活性物質部, 室長 (20192130)

Co-Investigator(Kenkyū-buntansha) OKAWARA Akiko  National Institute of Health, Bioactive, Mol., Res.Associate, 生物活性物質部, 研究員 (30260277)
SASAKI Tsuguo  National Institute of Health, Sefity Res., Lab Chief, 安全性研究部, 室長 (60142139)
YAMAKAWA Yoshio  National Institute of Health, Cell, Biochem., Senior Researcher, 細胞化学部, 主任研究官 (50100102)
Project Period (FY) 1993 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥800,000 (Direct Cost: ¥800,000)
Keywordsautoimmune disease, / myeloperoxidase, / MPO, / neutrophils, / ANCA, / glomerulonephritis / 腎炎 / リウマチ / ミエロパーオキシダーゼ / ミエロオパーオキシダーゼ / ミエロペルオキダーゼ
Research Abstract

In pauci-immune necrotizing crescentic glomerulonephritis (NCGN) autoimmune disease, anti myeloperoxidase (MPO) -antibody increase in peripheral blood of the patients.Determination of epitopes of anti-MPO antibody in some autoimmune diseases such as NCGN my give us a clue to the etiology and be used for prediction of the diseases.We have demonstrated three types of MPO (I,II,and III) and that some sera of GN reacted with the large subunit (59 kDa) of MPO-III,but not to the small subunit (14 kDa).As one serum of them most strongly reacts with a 55-kDa-deglycosylated form derived from the 59-kDa large subunit, we have attempted to prepare some recombinant the large fragments of large subunit.
In the present study, we prepared the recombinant MPO-fragments as panels to analyze epitope of serum of patient with autoimune disease.cDNA encoding 59 kDa-subunit (large) of MPO was amplified by PCR in 12 parts and these cDNAs were separately inserted into the vector.The recombinant MPO fragments were expressed in E.coli and were digested with guanidine hydrochloride in a sonicator.The fragments were purified with an affinity column chromatography.The obtained fragments were used for western blot analysis to determine the reactivity of sera of patients.Some sera reacted with the MPO fragments containing Met409.The results confirmed the recognition site in native MPO-III molecule by an anti-MPO serum is around sugar attachment sites in the N-terminus in the large subunit of MPO.

Report

(4 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • 1993 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Mohamed, A. et al.: "Production and characterrization of polyclonal anti-canine interleukin-8 antibodies." Immunology. (in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Saeki, T. et al.: "Significance of myeloperoxidase in rapidly progressive glomerulonephritis." Am. J. Kidney Dis. 26, 13-21, 1995.26. 13-21 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nagao, S. et al.: "Modification of delayed-type hypersensitivity reactions by muramyldipeptide in guine a pigs." FEMS Immunol. Med. Microbiol.11. 231-246 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsumoto, Y. et al.: "Morphological alteration of canine neutrophils induced with recombinant canine inter leukin-8." J. Toxicologic Pathol.8. 239-244 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Wang, C. -R. et al.: "T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thynmic selection: Requirement of calcineurin activation for thymic positive selction but not negative selection." J. Exp. Med.181. 927-941 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 中山俊憲,鈴木和男: "免疫・Immunology Frontier : 胸腺内T細胞とシグナル伝達" メディカルビュー社, 8 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki, K., Hosaska, S., Morikawa, K., Suzuki, M., Suzuki, S., Miyoshi, M., Fujita, M., and Mizuno, S.: "Bioimaging of myeloperoxidase release into phagolysosome of viable polymorphonuclear leukocytes and reaction of the enzyme with microspheres using a highly sensitive analyzer system." IMRAS.Bioimages. 1. 13-20 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hosokawa, Y., Kawaguchi, R., Hikiji, Yamada, M., Suzuki, K., Nakagawa, T., Yoshihara T., and Yamaguchi, K.: "Cloning and characterization of four types of cDNA encoding myeloperoxidase from human monocytic cell line SKM-1." Leukemia. 7. 441-445 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki, K., Yamakawa, Y., Matsuo, Y,, Kamiya, T., Minowada, J., and Mizuno, S.: "Isolation and amino acid sequence of a chemotactic protein, LECT/Interleukin 8, from a human myeloid leukemia cell line, ML-1." Immunol.Lett.36. 71-82 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tada, M., Sawamura, Y., Sakuma, S., Suzuki, K., Ohta, H., Aida, T., and Abe H.: "Cellular and cytokine responses in the human central nervous system to intra-cranialadministration of tumor necrosis factor-alpha for the treatment of malignant gliomas.Cancer Immunol." Immunother.36. 251-259 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tada, M., Suzuki, K., Yamakawa, Y., Sawamura, Y., Sakuma, S., and Abe H.: "Human glioblastoma cells produce 77 amino acid interleukin-8 (IL-8 77)." J.Neuro-Oncol.16. 25-34 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishikawa, J., Suzuki, S., Kunimoto, H., Hirota, Y., Mizuno, S.and Suzuki, K.: "Cloning of a canine gene homologous to the human interleukin-8-encoding gene." Gene. 131. 305-306 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shibata, M., Ohaka, T., Mizuno, S., and Suzuki, K.: "Characterization of a 64-kDa protein phosphorylated during chemotactic activation with IL-8 and fMet-Leu-Phe of human polymorphonuclear leukocytes.I.Phosphorylation of a 64-kDa and other proteins." J.Leukocyte Biol.54. 1-9 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Shibata, M., Yamakawa, Y., Ohoka, T., Mizuno, S., and Suzuki, K.: "Characterization of a 64-kDa protein phosphorylated during chemotactic activation with IL-8 and fMet-Leu-Phe of human polymorphonuclear leukocytes.II.Purification and amino acid anolysis of phosphorylated 64-kDa protein." J.Leukocyte Biol.54. 10-16 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Arimura, Y., Minoshima, S., Kamiya, Y., Tanaka, U., Nakabayashi, K., Kitamoto, K., Nagasawa, T., Sasaki, T., and Suzuki, K.: "Serum myeloperoxidase and serum cytokines in anti-myeloperoxidase antibody-associated glomerulonephritis." Clin.Nephrol.40. 256-264 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsumoto, Y., Mohamed, A., Onodera, T., Kato, H., Ohashi, T., Goitsuka, R., Tsujimoto, H., Hasegawa, A., Furusawa, S., Yoshihara, K., Ishikawa, J., Hotta, K., Suzuki, K., and Hirota, H.: "Molecular cloning and expression of canine interleukin 8 cDNA." Cytokine. 6. 455-461 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki, K., Yamano, M., Kawai, M., Nakajima, T., Ishida-Okawara, A., Yamagoe, S., Hatsu, M., Imai, S., Suzuki, M., Mizuno, S.and Hotta, K.: "Bioimaging analysis of a novel diketopiperadine (N-TAF1/SF2771) -induced nuclear change in neutrophil-adhered A549 lung carcinoma cells." Bioimages. 2. 149-154 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mohamed, A., Matsumoto, Y., Furusawa, S., Yoshihara, K., Matsumoto, Y., Suzuki, K., Onodera, T., and Hirota, Y.: "Production and characterrization of polyclonal anti-canine interleukin-8 antibodies." Immunology. (in press.).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Saeki, T., Kuroda, T., Morita, T., Suzuki, K., Arakawa, M., and Kawasaki, K.: "Significance of myeloperoxidase in rapidly progressive glomerulonephritis." Am.J.Kidney Dis.26. 13-21 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nagao, S., Kawabata, Y., Kitano, M., Suzuki, K., Nishikawa, T., and Takada, H.: "Modificaiton of delayd-type hypersensitivity reactions by muramyldipertide in guinea pigs.FEMS Immunol." Med.Microbiol.11. 231-246 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsumoto, Y., Matsumoto, Y., Onodera, T., Yamagoe, S., Suzuki, K., and Hirota, H.: "Morphological alteration of canine neutrophils induced with recombinant canine interleukin-8." J.Toxicologic Pathol.8. 239-244 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Wang, C.-R., Hashimoto, K., Kubo, S., Yokochi, T., Kubo, M., Suzuki, M., Suzuki, K., Tada, T., and Nakayama, T.: "T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thynmic selection : Requirement of calcineurin activation for thymic positive selction but not negative selection." J.Exp.Med.181. 927-941 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Arimura, Y., Minoshima, S., Nagasawa, T., and Suzuki, K.: "Serum IL-8, Soluble ICAM-1, glomerular expression of cellular adhesion molecules and myeloperoxidase (MPO) release from the neutrophils in MPO-ANCA associated crescentic glomerulonephritis (CRGN)." The 5 the International Workshop on ANCA,31 August-3 September, 1993, Cambridge, UK.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Saeki, T., Kawasaki, K., Kuroda, T., Morita, T., Nakano, M., Ohtani, I., Suzuki, K., and Arakawa, M.: "Significance of myeloperoxidase (MPO) in rapidly progressive glomerulonephpritis (RPGN)." 26th American Soc.of Nephrol.Nov.14-17,1993, Boston.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Nishimura.M., Arai, T., Yamagoe, S., and Suzuki, K.: "Production of monoclonal antibodies distinguishing two IL-8 family proteins, LUCT/IL-8 and MDNCF/IL-8, and recognizing both proteins." The 1993 ISICR meeting, Oct.24-28,1993, Tokyo.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ishikawa, J., Suzuki, S., Hotta, K., Hirota, Y., Mizuno, S., and Suzuki, K.: "Cloning of the gene encoding canine interleukin-8." The 1993 ISICR meeting, Oct.24-28,1993, Tokyo.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsumoto, Y., Mohamed, A., Onodera, T., Kato, H., Ohashi, T., Goituska, R., Tsujimoto, H., Hasegawa, A., Ishikawa, J., Hotta, K., Suzuki, K., and Hirota, Y.: "Molecular cloning and expression of canine interleukin-8 cDNA." The 1993 ISICR meeting, Oct.24-28,1993, Tokyo.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamagoe.S., Yamakawa, Y., Matsuo, Y., Minowada, J., Mizuno, S., and Suzuki, K.: "Idenitfication of a novel cheotactic protein for polymorphonuclear leukocytes produced by a human T cell leukemia cell line." The 1993 ISICR meeting, Oct.24-28,1993, Tokyo.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki, K.: "Myeloperoxidase as virucidal activity and antigen in autoimmune disease." International Congress on Reg. of Leukocyte Production and Immune Function.Dec.1-5,1993, Sydney.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Suzuki, K., Shiino, T., Hosokawa, Y., Yamagoe, S., Kuwahara, Y., Miyoshi-Koshio, T., Honda, M., Mizuno, S., Totani, M., Yamamoto, K.: "Satellite symposium on environmental factors and HIV :" Joint Scientific Meeting of theTenth International Conference on AIDS.Yokohama, a August 8,1994.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Fujii, A., Kenri, T., Yamagoe, S., Arimura, Y., Nagasawa, T., Mizuno, S., and Suzuki, K.: "Preparation of recombinant GST-MPO fragemts of E.coli for epitope analysis of anti-MPO in MPO-III ANCA." The 6th International ANCA Workshop Paris June 28-July 1,1995.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Arimura, et al.: "Pulmonary fibrosis in myeloperoxidase (MPO) specific antineutrophil cytoplasmic antibody (MPO-ANCA) related vasculitis." The 6th International ANCA Workshop Paris June 28-July 1,1995.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Minoshima, et al.: "Release of myeloperoxidase (MPO) neutrophils in MPO-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA) related glomerulonephritis." The 6th International ANCA Workshop Paris June 28-July 1,1995.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Matsumoto, Y., Hirota, Y., Yamagoe, S., Suzuki, K., Matsumoto, Y., and Onodera, T.: "Molecular cloning of canine interleukin 8 cDNA and cxpression of the recombinant protein."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hirota, Y., Yang, M.-P., Ohta, Y., Araki, S., Matsumoto, Y., Kang, C.-B.Mohamed, A., Yoshihara, K., Furusawa, S., Suzuki, K., Onodera, T., Akiyama, K., and Sugii, S.: usefull ness of egg whte derivatives (EWD) and recombinatn bovine interferon alpha (rBoIFNalphal) in veterinary medicine.in : Vaccines in agriculture immunological application to animal health and production (eds.Wood, P., Willadsen, P., Vercoe, J., Hoskinson, R., and Demeyer, D.). CSIRO press, Melbourne, Australia, 57-63 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mohamed, A. et al.: "Production and characterrization of polyclonal anti-canine interleukin-8 antibodies." Immunology. (in press). (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Saeki, T. et al.: "Significance of myeloperoxidase in rapidly progressive glomerulonephritis." Am. J. Kidney Dis. 26,13-21,1995.26. 13-21 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Nagao, S. et al.: "Modificaiton of delayed-type hypersensitivity reacthions by muramyldipeptide in guine a pigs." FEMS Immunol. Med. Microbiol.11. 231-246 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Matsumoto, Y. et al.: "Morphological alteration of canine neutrophils induced with recombinant canine interleukin-8." J. Toxicologic Pathol.8. 239-244 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Wang, C.-R. et al.: "T cell receptor-mediated signaling events in CD4+CD8+ thymocytes undergoing thynmic selection : Requirement of calcineurin activation for thymic positive selction but not negative selection." J. Exp. Med.181. 927-941 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 中山俊憲、鈴木和男: "免疫・Immunology Frontier :胸腺内T細胞選択とシグナル伝達" メデイカルビュー社,

    • Related Report
      1995 Annual Research Report
  • [Publications] Suzuki,K.et al.: "Bioimaging Analysis of a novel diketopiperadine(N-TAF1/SF2771)-indued nuclear change in neutrophil-adhered A549 lung carcinoma cells" Bioimages. 2. 149-154 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Chrong-Reen Wang,et al.: "TCR-mediated signaling events in CD4+CD8+thymocytes undrergoing thymic selection:Requirement of calcineurin activation for thymic positive selection but not negative" J.Exp.Med.in press.

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzuki,K.et al.: "Isolation and amino acid sequence of a chemotactic protein,LECT/Interleukin 8,from a human myeloid leukemia cell line,ML-1." Immunol.Lett.36. 71-82 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shibata,M.et al.: "Characterization of a 64-kDa protein phosphorylated during chemotactic activation with IL-8 and fMet-Leu-Phe of human polymorphonuclear leukocytes." J.Leukocyte Biol.54. 1-9 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shibata,M.et al.: "II.Purification and amino acid analysis of phosphorylated 64-kDa protein." J.Leukocyte Biol.54. 10-16 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Arimura,Y.,et al.: "Serum myeloperoxidase and serum cytokines in anti-myeloperoxidase antibody-associated glomerulonephritis." Clin.Nephrol.40. 256-264 (1993)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzuki,K.et al.: "Bioimaging of myeloperoxidase release into phagolysosome of viable polymorphonuclear leukocytes and reaction of the enzyme" Bioimages. 1. 13-20 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hosokawa,Y.et al.: "Cloning and characterization offour types of cDNA encoding myeloperoxidase from human monocytic cell line SKM-1." Leukemia. 7. 441-445 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Suzuki,K.et al.: "Isolation and amino acid sequence of a chemotactic protein.LECT/Interleukin 8,from a human myeloid leukemiacell line,ML-1." Immunol.Lett.36. (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Shibata,M.et al.: "Characterization of a 64-kDa protein phosphorylated during chemotactic activation" J.Leukocyte Biol.54. 1-9 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sibata,M.et al.: "II.Purification and amino acid analysis of phosphorylated 64-kDa protein." J.Leukocyte Biol.54. 10-16 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Arimura,Y.,et al.: "Serum myeloperoxidase and serumcytokines in anti-myeloperoxidase antibody-associated glomerulonephritis." Clin.Nephrol.40. 256-264 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] "ミエロパーオキシデース Myeloperoxidase(MPO)" 東京医学書院 腎臓key Notes長澤俊彦編, 353 (1992)

    • Related Report
      1993 Annual Research Report

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

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