KOMATSU Yutaka University of Tokyo,Faculty of Medicine,Fellow, 医学部(病), 医員
SHIINA Shuichiro University of Tokyo,Faculty of Medicine,Staff, 医学部(病), 助手
KAWASE Tateo University of Tokyo,Faculty of Medicine,Staff, 医学部(病), 助手 (40169727)
|Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥1,400,000 (Direct Cost: ¥1,400,000)
In the present study,cellular communication in the liver has been investigated in vivo or in vitro to clarify the role of hepatic sinusoidal cells in the pathogenesis of various liver diseases.
Isolation and culture of hepatic sinusoidal cells,such as Kupffer cells,pit cells and hepatic endothelail cells,have been established.Kupffer cells in primary culture are found to release various kinds of mediators such as lysosomal enzymes,prostaglandins, oxidatve radical intermediates and cytokines.Hepatic endothelial cells in primary culture showed their characteristic feature of pore and sieve plates.NK activity is demonstrated in Pit cells,one of organ associated NK cells.
In addition,Kupffer cells are found to release proliferating growth factor for hepatic endothelial cells.The mechanisms of cell growth was found to be mediated via protein kinase C.Molecular weight of the growth factor was less than 8-10kd, and this growth factor is sensitive to heat or trypsin treatment.
Mechanism of neutro
phil accumulation in the liver of alcoholics has been investigated,and we have demonstrated a proteinous chemotactic factor from the hepatocytes exposed to ethanol. Molecular weight of chemotactic factor is 20kd and 45kd.Further characteristic of these factors are now investigated,and one of these factor is cytokine.Furthermore,role of neutrophils in hepatic injury induced by galactosamine has been investigated,and we have clearly demonstrated that an increased amounts of TNF in circulation contribute to the mechanism of neutrophil-adhesion to hepatic endothelial cells. In vitro study revealed that an adhesion of neutrophils to hepatic endothelial cells are found to enhance in the presence of TNF,LPS,or PAF. These cytokines are found to show synergistic effect. After incubating with these cytokine,ICAM expression on hepatic sinusoidal endothelial cells was found to be enhanced.
Biological response modifier(BRM)enhanced an activity of liver associated NK cells,which protect against hepatic metastasis of colon carcinoma.An increase in NK activity was also mediated by Kupffer cell function,and activation of NK cells in the liver was enhanced by IL-2 released from macrophages and tissue macrophages(Kupffer cells). Therapeutic usage of BRM has been also investigated. Less