1991 Fiscal Year Final Research Report Summary
The Role of Hepatic Macrophages During Liver Regeneration.
| Project/Area Number |
02670293
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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 |
Gastroenterology
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| Research Institution | Faculty of Medicire, University of Tokyo |
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Principal Investigator |
HAYASHI Shigeki Facul. of Med. Univ. of Tokyo Assistant professor, 医学部(病), 助手 (20092299)
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| Co-Investigator(Kenkyū-buntansha) |
OHNO Akihiko Facul. of Med. Univ. of Tokyo Clinical fellowr, 医学部(病), 医員 (30223902)
SATOSHI Mochida Facul. of Med. Univ. of Tokyo Clinical fellow, 医学部(病), 医員 (20219968)
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| Project Period (FY) |
1990 – 1991
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| Keywords | Liver regeneration / Liver injury / Hepatic Macrophage / NBT / partial hepatectomy / C. Parvum / HGF / Cytokine |
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| Research Abstract |
The function of hepatic macrophage after partial hepatectomy and their contribution to liver injury and regeneration were studied in rats. The following results were obtained.
1) Using liver perfusion with nitro blue tetrazolium and phorbol myristate acetate, the function of hepatic macrophages in situ was found to be activated in their ability to produce cytokines from 24 to 72 hr following partial hepatectomy.
2) Such activation was attenuated by oral administration of polymyxin B sulfate, suggesting that gut-derived substances may contribute to the activation through overloading to the remaining liver.
3) Administration of a small amount of endotoxin after partial hepatectomy provoked massive hepatic necrosis due to sinusoidal fibrin deposition through excitation of these activated hepatic macrophages, as was seen in rats-pretreated with Cor-ynebacteriumparvum. However, the mechanism of development of sinusoidal fibrin deposition differed between both models ; superoxide anions or TNFA released from activated hepatic macrophages seemed to destroy directly endothelial cells in the Cor-ynebacterium parvum model, but other factors such as tissue factor to injure the function of endothelial cells leading to fibrin deposition in the hepatectomized model.
4) The increase in mitotic index in hepatocytes after partial hepatectomy was significantly reduced by administration of polymyxin B sulfate or gum arabic, polysaccharide of high molecular weight which blocks macrophage function, suggesting that activated hepatic macrophages may regulate liver regeneration.
From these observations, we conclude that hepatic macrophages may be activated after partial hepatectomy. Such macrophages may regulate liver regenaration and also contribute to development of liver injury.
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