EFFECT OF DEPLETION OF KUPFFER CELLS AND MACROPHAGES ON ACUTE REJECTION OF LIVER TRANSPLANTATION

背景和目的。我们研究了巨噬细胞和库普弗细胞在异体大鼠肝移植中延长移植物存活的作用。材料与方法。本研究分为5个实验组大鼠同种异体肝移植。ⅰ组和ⅴ组大鼠肝移植后静脉给予未处理的肝移植，ⅴ组大鼠肝移植后静脉给予脂质体包封双膦酸二氯乙烯6次。II组大鼠移植去库普弗细胞移植物。III组和IV组大鼠分别采用未处理的移植物和去库普弗细胞的移植物进行移植，两组大鼠在肝移植后均接受2次脂质体包膜二膦酸二氯乙烯注射。每天对这些动物进行检查，以确定它们的生存期。于第3、6、9、12、15、21、30天处死大鼠。结合肝组织病理学和免疫组织化学检查移植肝。在IV组，60%的移植物存活了100 ~ 150天。移植物存活时间明显长于其他各组。长期存活大鼠血清的过继移植对未作任何处理的大鼠心脏移植存活无影响。IV组长活大鼠对异体皮肤第二次移植无排斥反应。各组血清总胆红素水平、单核细胞数量、移植物ED2阳性细胞数量均逐渐升高，直至肝移植后2周，但IV组ED2阳性细胞数量在术后第12天开始减少。组织学上，ED2阳性细胞减少倾向于位于门静脉周围区域。这些结果表明，肝移植存活的延长可能是由于移植物中kupffer细胞的消耗和受体巨噬细胞向移植物迁移的结果。

Background and Aim. We examined the roles of kupffer cells and macrophages in the prolongation of graft survival in allogeneic rat liver transplantation.Materials and Methods. This study consisted of 5 experimental groups of rats underwent allogeneic liver grafts. The rats in Group I and V were transplanted with non-treated grafts, rats in Group V were administered with liposome encapsulated dichloromethylene bisphosphonate intravenously six times after liver transplantation. The rats in Group II were transplanted with kupffer cells-depleted grafts. The rats in Group III or IV were transplanted with non-treated grafts or kupffer cells-depleted grafts respectively, and both groups received twice injections of liposome encapsulated dichloromethylene diphosphonate after liver transplantation. The animals were examined daily to determine the survival period. The rats were killed on days 3, 6, 9, 12, 15, 21 and 30. The liver grafts were examined taking into account the liver histopathology and immunohistochemistry.Results. In Group IV, 60% of the grafts survived for >150 days. The graft survival periods were significantly longer than those of other groups. Adoptive transfer of serum of long survived rat did not affect the heart graft survival in rat, which underwent heart transplantation without any treatments. The long-survived rats of Group IV did not reject the second graft of allogeneic skin. Although the level of total serum bilirubin, the number of mononuclear cells and ED2 positive cells of grafts increased gradually until two weeks after liver transplantation in all group, the number of ED2 positive cells began to decrease on postoperative day 12 in Group IV. Histologically, the decrease of ED2 positive cells tended to be located around the periportal area.Conclusions. These findings suggested that the prolongation of liver graft survival could be result from the depletion of kupffer cells in liver graft and recipient macrophage migrating to the graft.