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

干枯细胞和巨噬细胞的消耗对肝移植急性排斥反应的影响

基本信息

批准号：
10557108
负责人：
DOI Hideyuki
金额：
$ 6.08万
依托单位：
TOHOKU UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

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.

背景和目的。我们研究了Kupffer细胞和巨噬细胞在延长同种异体大鼠肝移植存活时间中的作用。材料和方法。本研究包括5组同种异体肝移植大鼠。I组和V组大鼠移植未经处理的移植物，V组大鼠肝移植后静脉注射二氯亚甲基双膦酸脂质体6次。II组大鼠移植去库普弗细胞移植物。组III和组IV分别移植未经处理的移植物和去除枯否细胞的移植物，两组均于肝移植后两次注射脂质体包裹的二氯亚甲基二磷酸盐。每天对动物进行检查，以确定存活期。分别于第3、6、9、12、15、21、30天处死大鼠。对移植肝进行组织病理学和免疫组织化学检查。在IV组，60%的移植物存活150天。移植物存活期明显长于其他组。长期存活大鼠的血清过继转移不影响未经任何处理的大鼠心脏移植的存活。IV组长期存活大鼠对第二次同种异体皮肤移植无排斥反应。尽管所有组的血清总胆红素水平、单个核细胞数和移植物ED2阳性细胞数在肝移植后2周才逐渐升高，但IV组ED2阳性细胞数在术后第12天开始下降，组织学上看，ED2阳性细胞数的减少主要集中在门静脉周围。这些结果提示，移植肝存活时间的延长可能是由于移植物中枯否细胞的耗竭和受体巨噬细胞向移植物的迁移所致。