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Pancreatic protease and activation of leukocyte during MOF

Research Project

Project/Area Number 14571131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

MITSUOKA Hiroshi  Hamamatsu University School of Medicine, Second Department of Surgery, Assistant, 医学部附属病院, 助手 (10324360)

Co-Investigator(Kenkyū-buntansha) UNNO Naoki  Hamamatsu University School of Medicine, Second Department of Surgery, Lecturer, 医学部附属病院, 講師 (20291958)
SUZUKI Shohachi  Hamamatsu University School of Medicine, Second Department of Surgery, Lecturer, 医学部附属病院, 講師 (20196827)
NAKAMURA Satoshi  Hamamatsu University School of Medicine, Second Department of Surgery, Professor, 医学部, 理事 (00090027)
Project Period (FY) 2002 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Keywordsintestinal ischemia / shock / leukocyte / protease / multiple organ failure / 活性化因子 / 腹水 / 活性化 / 小腸
Research Abstract

Pancreatic enzymes in the ischemic intestine are involved in the production of in vivo inflammatory mediators. These mediators stimulate cells in the cardiovascular system during shock and initiate multiorgan failure. An important aspect that controls the extent of the inflammation is the dispersion of these mediators from the ischemic intestine. In the past, two pathways for dispersion of these inflammatory mediators have been identified, absorption into the intestinal venous circulation and uptake into the lymphatics. We hypothesize here that the inflammatory mediators produced by pancreatic digestive enzymes in the lumen of the intestine may also be released directly into the peritoneal space. To assess the presence of inflammatory mediators in the peritoneal cavity in response to splanchnic arterial occlusion (90 min) and reperfusion (SAO shock), we measured the ability of fluid collected from this cavity to activate naive donor granulocytes. After SAO in control rats, peritoneal lavage fluid caused activation of naive donor granulocytes when tested in vitro. In contrast, when the lumen of the small intestine was flushed with a broad-acting pancreatic enzyme inhibitor (6-amidino-2-naphtyl p-guanidinobenzoate dimethanesulfate), the fluid no longer caused leukocyte activation. Reduction of the levels of inflammatory mediators in the peritoneal fluid was associated with an attenuation in the fall of blood pressure after SAO shock. These results indicate that the inflammatory mediators, which are produced by pancreatic digestive enzymes, can be absorbed directly into the systemic circulation via a transperitoneal route and play a part in the development of multiorgan failure.

Report

(4 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • 2002 Annual Research Report

Research Products

(4 results)

All 2004

All Journal Article (4 results)

  • [Journal Article] Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion2004

    • Author(s)
      Ishimaru K, Mitsuoka H, et al.
    • Journal Title

      Shock 22

      Pages: 467-471

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pancreatic proteases and inflammatory mediators in peritoneal fluid during splanchnic arterial occlusion and reperfusion.2004

    • Author(s)
      Ishimaru K, Mitsuoka H, et al.
    • Journal Title

      Shock 22

      Pages: 467-471

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Pancretatic Proteases and Inflamatory Mediators in Peritoneal Fluid During Splanchnic Arterial Occlusion2004

    • Author(s)
      Kei Ishimaru, Hiroshi Mitsuoka, et al.
    • Journal Title

      Shock 22(5)

      Pages: 467-471

    • Related Report
      2004 Annual Research Report
  • [Journal Article] ショックと腸管内プロテアーゼ2004

    • Author(s)
      三岡博
    • Journal Title

      医薬の門 44(3)

      Pages: 197-199

    • Related Report
      2004 Annual Research Report

URL: 

Published: 2002-03-31   Modified: 2016-04-21  

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