| Project/Area Number |
04670739
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
FURUKAWA Kenichirou Kyusyu Univ.Faculty of Med.Lecturer, 医学部, 助手 (80209163)
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| Co-Investigator(Kenkyū-buntansha) |
IWAMOTO Takuya Kyusyu Univ.Faculty of Med.attending doctor, 医学部, 医員
TORISU Motomichi Kyusyu Univ.Faculty of Med.assistant professor, 医学部, 助教授 (90038810)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | septic-MOF / Hepatic injury / Neutrophil / Adhesion molecule / Complement / Hepatic macrophage / Shwartzman reaction / Endotoxin tolerance |
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| Research Abstract |
This study was undertaken to clalify the pathogenesis of septic MOF, measuring the functional changes in neutrophils and complement system by means of clinical samples, and then investigating the functional changes of hepatic and splenic macrophages in septic animal models .
Neutrophils isolated from the patients with septic MOF showed enhanced endotherial cell adhesion with up-reguration of adhesion molecules such as CR3, increased oxygen radical generation, and increased lysosomal enzyme release. In further study about the activatin of complement in these patients, it was demonstrated that the serum concentrations of CH50 and C4 decreased and the plasma concentrations of C3a and C4a increased. These result suggested that the activation of neutrophils and complement system causes endotherial cell injury and induces organ failure in septic MOF.
In rabbit generalized Shwartzman reaction model with 2 times lipopolysaccalide injection, peripheral neutrophils showed significantly enhanced endotherial cell adhesion. In rat endotoxin tolerance model with several times LPS intraperitoneal injection, peripheral neutrophils were inactivated. Furthermore hepatic and splenic macrophages were activated , releasing toxic mediators such as nitric oxide and caused hepatic injury in sepsis models.
Taken together, our study demonstrated that increased neutrophil adhesion to endotherial cells possibly through complement activation play an important role in the pathogenesis of septic MOF.Moreover activation of hepatic and splenic macrophages is an another factor which causes hepatic injury.
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