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Pathogenesis of cytomegalovirus infection after organ transplantation

Research Project

Project/Area Number 10671136
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionTokai University

Principal Investigator

TANAKA Kazuo  Tokai University, School of Medicine, Dept.of Infectious diseases, Associate Professor, 医学部, 助教授 (50236569)

Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1999: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordscytomegalovirus / organ transplantation / latent infection / nitric oxide / bronciolar epithelial cells / nitrotyrosine / T cell signal transduction / 間質性肺炎
Research Abstract

Cytomegalovirus (CMV)-associated pneumonitis (CMV-P) is a major complication in organ transplant recipients, although its pathogenesis has been still unclear. This research was organized to solve this problem. In 1998-1999, the following results were obtained.
1. (C3HxBALB/c) F1 mice, which had been inoculated with 0.2 LD50 of murine cytomegalovirus (MCMV) at 4 wk before, were injected with parental spleen cells to induce GVH. Thereafter, MCMV-DNA could be detectable in the lungs and hearts in Nitric Oxice (NO)-dependent manner, suggesting that NO played a role in MCMV reactivation. However, such emergent DNA was not transferred to RNA. Thus, other factor(s) may be required for the full reactivation of latent MCMV.
2. Four weeks after intraperitoneal inoculating of 0.2 LD50 (50% lethal dose) of (MCMV) in adult BALB/c mice or in (C57BL/6xSv129) F1 mice, CMV-P was evoked by a single injection of anti-CD3 mAb in the lungs free of the virus. In immunohistochemistry, nitrotyrosine was detected in the bronchioepithelial cells, suggesting that the cells were targeted in our model of CMV-P. In contrast, CMV-P could not be induced in inducible Nitric Oxidase Synthetase knock-out (iNOS KO) mice.
3. In in vitro assay, T cells from MCMV-infected mice, in which the virus was detected only in the salivary glands, were revealed not to be induced termination signals upon anti-CD3 stimulation. This may be the why MCMV-infected mice produced higher amounts of cytokines upon anti-CD3 stimulation in vivo, than those of uninfected control mice.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (26 results)

All Other

All Publications (26 results)

  • [Publications] 田中和生: "サイトメガロウイルス感染症成立における宿主側要因"日本臨床. 56. 97-101 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田中和生: "GVHにより惹起される潜伏サイトメガロウイルスの再活性化におけるNOの役割"今日の移植. 11. 561-566 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sawamura, S et al: "The role of intestinal bacterial flora in the tuning of the T cell reperoire"Immunology. 201. 120-132 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu, K et al: "Induction of glomerular lesions in the kidneys of mice infected with Vero-toxin-producing Escherichia coli by Lipopolysaccharide injection"The Journal of Infectious Diseases. 180. 1374-1377 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 澤村貞昭 他: "腸管出血性大腸菌O157に対する抗生物質の有効性に関する検討"感染症学雑誌. 73. 1054-1063 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada, K et al.: "Nitric oxide increases the amount of murine cytomegalovirus-DNA in mice latently infected with the virus."Archives of Virology. 144. 2273-2290 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 野田敏司 他: "GVHDにおけるサイトメガロウイルス再燃の機序. Annual Review免疫."中外医学社(東京). 7 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 田中和生: "食と生体防御-腸内細菌と食物アレルギーの制御-"菜根出版(東京). 23 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka, K.: "The role of the host's immune system in the pathogenesis of cytomegalovirus-associated disease"Nihon-Rinsho. Vol.56(in Japanese, abstract in English). 97-101 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka, K.: "The role of nitric oxide generated in graft -versus-host reaction in the reactivation of the latently-infected cytomegalovirus"Transplantation Now. Vol.11(in Japanese, abstract in English). 561-566 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sawamura, S. et al.: "The role of intestinal bacterial flora in the tuning of the T cell repertoire."Immunobiol. Vol.201. 120-132 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Shimizu, K. et al.: "Induction of glomerular lesions in the kidneys of mice infected with Vero-toxin producing Escherichia coli by Lipopolysaccharide injection"Infect. Immun.. Vol.180. 1374-1377 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sawamura, S. et al.: "Therapeutic effects of antibiotics against enterhemorrhagic Eschericia coli (EHEC)"The Journal of the Japanese Association for Infectious Diseases. Vol.73(in Japanese, abstract in English). 1054-1063 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Okada, K. et al.: "Nitric oxide increases the amount of murine cytomegalovirus-DNA in mice latently infected with the virus."Arch. Virol.. Vol.144. 2273-2290 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Noda, S. et al.: "Reactivation of Latently-infected cytomegalovirus in graft-versus-host reaction. "Annual review Menneki 2000""Chugai-Igakusha, Tokyo (in Japanese). 7 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Tanaka, K.: "Regulation of Food allergy by intestinal bacterial flora. "Shoku-to-Seiraibougyo""Sikon suppan, Tokyo(in Japanese). 23 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Sawamura, S et al: "The role of intestinal bacterial flora in the tuning of the T cell reperoire"Immunobiology. 201. 120-132 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Shimizu, K et al.: "Inductionof glomerular lesions in the kidneys of mice infected with Vero-toxin-producing Escherichia coli by Lipopolysaccharide injection"The Journal of Infectious Diseases. 180. 1374-1377 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Okada, K et al.: "Nitric oxide increases the amount of murine cytomegalovirus-DNA in mice latently infected with the virus"Archives of Virology. 144. 2273-2290 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 澤村貞昭 他: "腸管出血性大腸菌O157に対する抗生物質の有効性に関する検討-無菌マウスを用いた検討-"感染症学雑誌. 73巻10号. 1054-1063 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 野田敏司 他: "GVHDにおけるサイトメガロウイルス再燃の機序.Annual Review 免疫."中外医学社(東京). 7 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Kohda,T.Tanaka et al.: "Role of apoptosis induced by Helicobacter pylori infection in the development of duodenal ulcer" Gut. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] 澤村,貞昭・田中和生: "GVH反応に及ぼす腸内細菌叢(特にグラム陰性桿菌)の影響" 今日の移植. 11巻1号. 85-88 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中和生: "サイトメガロウイルス感染症成立における宿主側要因" 日本臨床. 56巻1号. 97-101 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中和生: "GVHにより惹起される潜伏サイトメガロウイルスの再活性化におけるNOの役割" 今日の移植. 11巻5号. 561-566 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 田中和生(分担): "食と生体防御" 菜根出版, 23 (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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