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

背景和目标。我们研究了枯否细胞和巨噬细胞在异基因大鼠肝移植中延长移植物存活的作用。本研究包括5个实验组的大鼠进行同种异体肝移植。I组和V组大鼠移植未经处理的移植物，V组大鼠在肝移植后静脉注射脂质体包封的二氯亚甲基二膦酸盐6次。第二组大鼠移植去枯否细胞移植物。第III组和第IV组分别移植未经处理的肝移植物和去除枯否细胞的肝移植物，两组均在肝移植后两次注射脂质体包封的二氯亚甲基二膦酸盐。每天检查动物以确定存活期。在第3、6、9、12、15、21和30天处死大鼠。对移植肝进行组织病理学和组织化学检查。在第四组中，60%的移植物存活>150天。移植物存活时间明显长于其他各组。长期存活大鼠血清连续输注对未经任何处理的大鼠心脏移植存活无影响。第四组长期存活的大鼠对第二次同种异体皮肤移植无排斥反应。各组血清总胆红素水平、单个核细胞数及移植肝ED2阳性细胞数均在术后2周逐渐升高，但Ⅳ组移植肝ED2阳性细胞数在术后12天开始下降。在组织学上，ED 2阳性细胞的减少倾向于位于门静脉周围。这些结果表明，移植肝存活时间的延长可能是由于移植肝枯否细胞的耗竭和受体巨噬细胞向移植肝迁移所致。

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.