Implication of intestinal lymphocytes in endotoxin-induced hepatic injury after partial hepatectomy in rats
| Project/Area Number | 15591396 |
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
NAKAMURA Toshio Hamamatsu University School of Medicine, Second department, Assistant Professor, 医学部附属病院, 講師 (40283353)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUK Shohachi Hamamatsu University School of Medicine, Second department, Assistant Professor, 医学部, 助教授 (20196827)
NAKAMURA Satoshi Hamamatsu University School of Medicine, Second department, Director, 医学部, 理事 (00090027)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed(Fiscal Year 2005)
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| Budget Amount *help |
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 2005 : ¥700,000 (Direct Cost : ¥700,000)
Fiscal Year 2004 : ¥1,000,000 (Direct Cost : ¥1,000,000)
Fiscal Year 2003 : ¥1,500,000 (Direct Cost : ¥1,500,000)
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| Keywords | hepatectomy / lipopolysaccharide / B lymphocyte / immunoglobulin M / complement / 腸管リンパ球 / IEL / 肝切除 / LPS / B cell / 補体 / エンドトキシン / 末梢リンパ球 |
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| Research Abstract |
Lymphocyte population constitutes major defense mechanism against endotoxemia, but the role of B lymphocytes in endotoxin-induced hepatic injury after hepatectomy is not clear. We employed lymphopenic (L(-)) rats by single administration of anti-rat lymphocyteserum, nu/nu athymic (T(-)) rats, B cell-ablated (B(-))rats by intermittent injection of anti-immunoglobulin (Ig) m-chain from birth, and their vehicle controls. These animals weresubjected to two-thirds hepatectomy with subsequent intravenous lipopolysaccharides (LPS, 1.5mg/kg) administration. The survival rate, plasma alanine transaminase (ALT), tumor necrosisfactor-a (TNF-α) and IgM levels, and total hemolytic activity (CH50) were determined. Hepatictissue deposition of IgM or C3 was assessed with immunohistochemistry. Results. The 24-hour survival rate in control animals was 20%, whereas those in L(-), T(-), and B(-) animals were 80%,0% and 100 %, respectively. Lymphocyte-sufficient control (L(+)) and Bcell-sufficient control (B(+)) animals showed a rapid elevation of plasma TNF-a levels 1 hour after the challenge, followed by an increase in plasma ALT levels. In B(+) group, plasma IgM levels were increased and CH50 activities were decreased 4 hours after LPS injection with significant difference compared to those at time 0. Liver histology showed massive hepatic necrosis with a dense accumulation of IgM and C3 deposits 4 hours after LPS administration. B cell ablation significantly ameliorated plasma ALT, IgM and CH50 levels, showing less histological liver damage. Conclusion. B lymphocytes susceptible to LPS might be implicated in the development of endotoxin-induced hepatic injury after partial hepatectomy. The result of our research will be published in Journal of Surgical Research.
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Report
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Research Products
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