| Project/Area Number |
05670495
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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 | Department of Internal Medicine, School of Medicine, Keio University |
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Principal Investigator |
ODA Masaya Sch.of Med.Keio Univ.Dept.of Int.Med.Assist.Prof., 医学部, 専任講師 (20129381)
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| Co-Investigator(Kenkyū-buntansha) |
FUNATSU Kazuo Sch.of Med.Keio Univ.Dept.of Int.Med.Assist.Prof., 歯学部, 助教授 (00129644)
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| Project Period (FY) |
1993 – 1995
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| Project Status |
Completed (Fiscal Year 1995)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | liver cirrhosis / hepatic sinusoidal endothelial cells / hepatic stellate cells (Ito cells) / Kupffer cells / Ca^<++> -calmodulin-actomyosin system / electron microscopy / Fura-2AM / FITC labelled endotoxin / prostaglandin (PG) E1 / endothelin (ET) -1,3 / 肝類洞内皮細胞 / 伊東細胞 / 細胞質内遊離カルシウムイオン / Ca^<++>-ATPase / 肝類洞血流 / 肝硬変 / Kupffer細胞 / 収縮運動 / endothelia / nitric oxide / 超微速度映画 / アクチン / 遊離カルシウムイオン / カルモデュリン / 電子顕微鏡 |
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| Research Abstract |
By transmission electron microscopy and immunohistochemistry, actin and myosin filaments and Ca^<++>-calmodulin actomyosin system are evident in the hepatic sinusoidal endothelial cells, hepatic stellate cells (Ito cells) and Kupffer cells. Immunohistochemistry and the dynamic analysis of intracytoplasmic free Ca^<++> ion using Fura2-AM showed that the Ca^<++> -calmodulin actomyosin system regulates the contraction and dilatation of the sinusoial endothelial fenestrae (SEF), contaction of Ito cells and phagocytotic activities of Kupffer cells.
Scanning and transmission electron microscopy revealed that the diameter and numbers of the SEF were significantly decreased concomitant with the fibrosis within the space of Disse in cirrhotic liver.
By quantitative analysis, the phagocytotic activity of Kupffer cells against the FITC-labelled endotoxin have been shown to be significantly decreased in cirrhotic liver. Furthermore, electron microscopic observations have proved that the microparticles injected via a mesenteric vein catheter are decreased in space of Disse in cirrhotic liver as compared with control liver.
These finding may indicate that the enhancement of a decrease of hepatic sinusoidal blood flow results from a decrease of SEF in diameter and number and a decrease of phagocytotic activity of Kupffer cells, both of which have some relationship with an increase of serum endotoxin levels in cirrhotic liver.
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