Effect of elimination of donor Kupffer cells and/or recipient macrophages on acute rejection in liver transplantation.
Effect of elimination of donor Kupffer cells and/or recipient macrophages on acute rejection in liver transplantation.
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发表时间：
2003-07
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通讯作者：
Y. Akamatsu;N. Ohkohchi;H. Doi;S. Satomi
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作者：
Y. Akamatsu;N. Ohkohchi;H. Doi;S. Satomi
背景/目的 Kupffer 细胞/巨噬细胞在肝移植后急性排斥反应中发挥抗原呈递和细胞因子产生的关键作用。在本研究中，我们尝试通过给予脂质体封装的 LE-Cl2MDP（二氯亚甲基二磷酸盐）来消除供体库普弗细胞和/或受体巨噬细胞，以澄清库普弗细胞和巨噬细胞耗竭对急性排斥反应的影响。方法 为了比较存活率，准备了五组：i）非治疗组，ii）Kupffer 细胞消除组：移植的 Kupffer 细胞消除移植物，iii）肝移植后给药组：未处理的移植物肝移植后注射 LE-Cl2MDP 两次，iv）额外给药组：移植的 Kupffer 细胞消除移植物并在肝移植后注射 LE-Cl2MDP 两次，v）肝移植后频繁给药组：注射 LE-Cl2MDP未经治疗的肝移植后每天一次，持续一周。进行肝功能检查、组织学检查、库普弗细胞和巨噬细胞的组织化学染色。结果 移植物的库普弗细胞消除或受体迁移巨噬细胞的消耗并没有延长存活天数。另外，在移植物的库普弗细胞和受体的迁移巨噬细胞均被消除的给药组中，移植物的存活时间显着延长。但发现高胆红素血症、肝纤维化和轻微的单核细胞浸润。结论 这些结果表明供体库普弗细胞和受体巨噬细胞在肝移植的急性排斥反应中发挥重要作用。
BACKGROUND/AIMS Kupffer cells/macrophages have pivotal roles of antigen presentation and cytokine production in the acute rejection after liver transplantation. In this study, we attempted to eliminate donor Kupffer cells and/or recipient macrophages by administration of liposome encapsulated LE-Cl2MDP (dichloromethylene diphosphonate) for clarification of the effect of depletion of Kupffer cells and macrophages on acute rejection. METHODOLOGY To compare the survival, five groups were prepared: i) non-treatment group, ii) Kupffer cells eliminated group: transplanted Kupffer cells eliminated graft, iii) administration after liver transplantation group: injected LE-Cl2MDP twice after liver transplantation of non-treated graft, iv) additional administration group: transplanted Kupffer cells eliminated graft and injected LE-Cl2MDP twice after liver transplantation, and v) frequent administrations after liver transplantation group: injected LE-Cl2MDP every day for one week after liver transplantation of non-treated. Liver function tests, histological examination, histochemical staining of Kupffer cells and macrophages were carried out. RESULTS Survival days were not prolonged by Kupffer cells elimination of the graft or by depletion of migrated macrophages of recipient. In additional in the administration group, in which both Kupffer cells of the graft and migrated macrophages of recipient were eliminated, graft survival was prolonged significantly. But hyper bilirubinemia, hepatic fibrosis, and slight mononuclear cell infiltration were recognized. CONCLUSIONS These results suggested that both donor Kupffer cells and recipient macrophages play important roles in acute rejection in liver transplantation.