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Role of polymorphonuclear neutrophil (PMN) cell death in inflammation and infection

Research Project

Project/Area Number 09470245
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionUniversity of Tokyo

Principal Investigator

SAITO Hideaki  Univ.of Tokyo, Faculty of Medicine Assistant professor, 医学部・附属病院, 助教授 (30134555)

Co-Investigator(Kenkyū-buntansha) FURUKAWA Satoshi  Univ.of Tokyo, Faculty of Medicine Clinical Associate, 医学部・附属病院, 医員
韓 一秀  東京大学, 医学部・附属病院, 医員
INOUE Tomomi  Univ.of Tokyo, Faculty of Medicine Clinical Associate, 医学部・附属病院, 医員
HAN Ilsoo  Univ.of Tokyo, Faculty of Medicine Clinical Associate
井上 知巳  東京大学, 医学部・附属病院, 医員
深柄 和彦  東京大学, 医学部・附属病院, 医員 (70323590)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥13,000,000 (Direct Cost: ¥13,000,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥10,300,000 (Direct Cost: ¥10,300,000)
Keywordsneutrophil / apoptosis / necrosis / infection / cytokine / reactive oxygen intermediates / growth hormone / CD16 / 炎症性メジエータ / 外科侵襲 / 細胞死 / apoptosis / necrosis / 接着分子
Research Abstract

We investigated the role of polymorphonuclear neutrophil(PMN)cell death in inflammation and infection, and obtained the following findings :
(1) PMNs from healthy volunteers were cocultured with or without live E.coli at different ratios. The PMNs were then analyzed by flow cytometry for cell death, reactive oxygen intermediates (ROI) production, and CD16 expression. Morphologic features also were assessed. PMN apoptosis was confirmed by DNA gel electrophoresis. TNF-alpha, IL-1beta and IL-6 levels in cell free supernatants were also measured. Low doses of E.coli inhibited PMN apoptosis. In contrast, a high dose of E.coli increased PMN necrosis. The mean percentages of PMN apoptosis after coculture with E.coli showed significant inverse correlations with cytokine levels in cell free supernatants. While ROI production increased after coculture with E.coli, CD16 expression decreased after coculture with E.coli.
(2) PMNs were cultured with various kinds of cytokines including TNF-alpha, IL-1 … More beta, IL-6, IL-8, GM-CSF and IL-10. Then, PMN cell death was assessed. While low dose of TNF-alpha inibited PMN apoptosis, high dose of TNF-alpha increased PMN apoptosis. IL-1beta, IL-6 and GM-CSF inhibited PMN apoptosis. IL-10 attenuated PMN apoptosis inhibition by IL-6.
(3) PMNs were pretreated with GH (0 or 100 ng/mL) for 3 hours, then cultured for 0, 4 or 12 hours and PMNs were analyzed by flow cytometry for cell death, ROI production, CD16 and Fas expression. GH inhibited PMN apoptosis at 12 hours of culture. GH enhanced ROI production by PMNs, and GH decreased Fas expression on PMNs.
(4) Peripheral blood samples were collected from patient before surgery, on day 1, 3, and 7 after surgery. Peritoneal samples were obtained aseptically through abdominal drain on day 1, 2 and 3 after surgery. PMNs were analyzed by flow cytometry for cell death. Peripheral PMN apoptosis was inhibited on day 1 and 3, and increased on day 7 after surgery. Peritoneal PMN apoptosis also was inhibited on day 1 after surgery, and significantly increased by days 3.
These findings suggest that augmented PMN bactericidal function, via inhibition of PMN cell death, may be beneficial for host defense against bacterial infection and/or sepsis. Less

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] S.Furukawa,et al.: "Glutamine-enriched enteral diet enhances bacterial clearance in pro traeted bacterial peritonitis, regardless of glutamine form" JPEN. 21. 208-214 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] S.Furukawa, et al.: "Glutamine-enriched bacterial killing by neutrophils from postoperative patients" Nutrition. 13. 863-869 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Fukatsu,et al.: "Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while in creasing adhesion in renote organs in peritonitis" J.Surg.Res. 68. 79-86 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] MT.Lin,et al.: "Preoperative total parenteral a nutrition(TPN)influence S postopera-tive systemia cytokine responses after colorectal eurgery" Nutrition. 13. 8-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Fukatsu,et al: "Nitric oxide donar decreases neutrophil adhesion in both ling and peritoneum during peritonitis" J.Surg.Res.74. 119-124 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furukawa S,Saito H,Inaba T,Lin MT,Inoue T,Naka S,Fukatsu K,Hashiguchi Y,Han I,Matsuda T,Ikeda S,Muto T.: "Glutamine-enriched enteral diet enhances bacterial clearance in protracted bacterial peritonitis, regardless of glutamine form." JPEN. 21. 208-214 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Furukawa S,Saito H,Fukatsu K,Hashiguchi Y,Inaba T,Lin MT,Inoue T,Han I,Matsuda T,Muto T.: "Glutamine-enhanced bacterial killing by neutrophils from postoterative patients." Nutrition. 13. 863-869 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukatsu K,Saito H,Han I,Furukawa S,Hashiguchi Y,Lin MT,Matsuda T,Inaba T,Inoue T,Ikeda S,Yasuhara H,Muto T.: "Nitric oxide inhibition decreases neutrophil adhesion at the inflammatory site, while increasing adhesion in remote organs in peritonitis." J Surg Res. 68. 79-86 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Lin MT., Saito H,Fukushima R,Inaba T,Fukatsu K,Inoue T,Furukawa S,Han I,Matsuda T,Muto T.: "Preoperative Total Parenteral Nutrition (TPN) Influences Postoperative Systemic Cytokine Responses After Colorectal Surgery." Nutrition. 13. 8-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Fukatsu K,Saito H,Han I,Furukawa S,Lin MT,Matsuda T,Ikeda S,Inoue, T,Yasuhara H,Muto T.: "Nitric oxide donar decreases neutrophil adhesion in both lung and peritoneum during peritonitis." J Surg Res. 74. 119-124 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] T.Matsuda,et al: "Growth hormone inhibits apoptosis and upregulates reactive oxygen intermediates production by human polymorphc muclear neutrophils" JPEN. 22. 368-374 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Inoue,et al.: "Effects of Growth horoncne and insulin-likegrowth factor Ion opsonin receptor expression onlocal and systemic phagecytes in a lethal peritonitis model" Crit Care Med. 26. 338-343 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] H.Saito: "Anabolic agents in trauma and Sepsis:Repleting body mass and function" Nutrition. 14. 554-556 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.Inoue,et al.: "Effects of growth hormone and insulin-like growth factor I on opsonin receptor expression on local and systemic pはgocyres in a lethal peritonitis model" Crit Care Med. 26. 338-343 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Furakawa, et al.: "Glutamine-enriched bacterial killing by neutrophils from postoperative patients." Nutrition. 13. 863-869 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Fukatsu, et al.: "Nitric oxide inhibition decreases neutrophit adhesion at the inflammatory site,while increasing adhesion in remote organs in peritonitis" J Surg Res. 68. 79-86 (1997)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2017-03-29  

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