1994 Fiscal Year Final Research Report Summary
Inhibition of Rejection Reaction by Modulating Actions of Adhesion Molecules on Sinusoidal Endothelial Cells in Rat Liver Allograft.
| Project/Area Number |
05670509
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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 | University of Occupational & Environmental Health (U.O.E.H.) |
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Principal Investigator |
YAMADA Shinwa U.O.E.H., Medicine, Assoc.Professor, 医学部, 助教授 (60143426)
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| Co-Investigator(Kenkyū-buntansha) |
TANAKA Yoshiya U.O.E.H., Medicine, Assist.Professor, 医学部, 助手 (30248562)
ETO Sumiya U.O.E.H., Medicine, Professor, 医学部, 教授 (90010347)
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| Project Period (FY) |
1993 – 1994
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| Keywords | liver transplant / ischemia-reperfusion injury / adhesion molecule / neutrophil / endothelial injury / platelet / interleukin-8 / hepatocyte growth factor |
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| Research Abstract |
In this study we have investigated into roles of adhesion molecules and chemokines in rejection reaction. It is thought from a therapeutic point of view that there are two important phases ; neutrophil-adhesion to the endothelial cells immediately after reperfusion, and T cell-adhesion in acute rejection.
I.Hepatic Injury after Ischemia-Reperfusion
1.in vitro
When rat liver was exposed to ischemia-reperfusion, serum IL-8 levels were immediately elevated and peaked at 6 hr after the reperfusion. The elevation was completely inhibited by inactivation of Kupffer cells.IL-8 mRNA was detected by Northern blot in the Kupffer cells isolated from the rat liver after the reperfusion, but was not detected in the control. These findings imply that IL-8 was derived from the activated Kupffer cells.
2.in vitro
It has been reported that platelet plays an important role in hepatic injury after reperfusion. Thus in an in vitro study a possible role of platelet in neutrophil-adhesion was investigated. It wa
… More
s demonstrated that in an early phase of inflammation platelet stimulated by thrombin adhered to unstimulated endothelial cells (HUVEC) via Gp IIb/IIIa, and thereafter neutrophils were tethered by P-selectin on the platelet. The similar experiment using sinusoidal endothelial cells is under consideration.
II.Possible roles of hepatocyte growth factor (HGF) in rejection reaction of rat liver allograft
We have demonstrated in an in vitro study that HGF promotes adhesion and migration of CD4 memory T-cells, and have proposed that it may contribute to induction of T cell-infiltration in the liver. Thus, we evaluated HGF level in the serum and the liver during the process of rejection reaction of rat liver allograft (ACI-Lewis), as comparing with those of donor specific tolerant (DST) group as the control. Serum HGF levels were significantly increased in DST as compared with those of the rejected group.In the liver of DST group, HGF was strongly expressed in the mononuclear cells in the portal areas, and there was infiltation of CD4 T-cells in the hepatic lobule. On the other hand, the liver of the rejected group showed HGF expression scattering in the hepatic lobules and the portal area surrounding the bile ductule. These results suggested possible roles of HGF in rejection reaction as follows : (1) it promotes hepatocyte regeneration (2) it induces CD4 T-cell migration in the liver (3) it stimulates proliferation of bile ductule cells. Less
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[Publications] Yamada, S., Mochida, S., Ohno, A., Hirata, K., Ogata, I., Ohta, Y., Fujiwara, K.: "Evidence for enhanced secretory function of hepatic macrophage after long-term ethanol feeding in rats." Liver. 11. 220-224 (1991)
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[Publications] Tomiya, T., Tani, M., Yamada, S., Hayashi, S., Umeda, N., Fujiwara, K.: "Serum hepatocyte growth factor levels in hepatectomized and nonhepatectomized surgical patients." Gastroenterology. 103. 1621-1624 (1994)
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[Publications] Tani, M., Tomiya, T., Yamada, S., Hayashi, S., Yahata, K., Akiyama, M., Kawai, S., Masaki, N., Fujiwara, K., Oda, T.: "Regulating factors of liver regeneration after hepatectomy." Cancer Chemother.Pharmacol.33. 29-32 (1994)
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[Publications] Adams, D.A., Havsath, L., Bottaro, D.P., Interrate, R., Catalano, G., Tanaka, Y., Strain, A., Hubscher, S.: "Hepatocyte growth factor and MIP-1beta : Structurally distinct cytokines that induce rapid cytoskeletal changes subset-preferential migration of T cell." Proc.Natl.Acad.Sci.USA.92. 7144-7148 (1994)
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[Publications] Mori, N., Yamashita, U., Tanaka, Y., Nakata, K., Oda, S., Morimoto, I., Eto, S.: "Interleukin-4 induces proliferation of adult T-cell leukemia cells." Eur.J.Haematol.50. 133-140 (1993)
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