PATHOGENIC ROLE OF KUPFFER CELL ACTIVATION IN THE REPERFUSION INJURY OF COLD-PRESERVED LIVER
PATHOGENIC ROLE OF KUPFFER CELL ACTIVATION IN THE REPERFUSION INJURY OF COLD-PRESERVED LIVER
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DOI：
10.1097/00007890-199411270-00003
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发表时间：
1994-11-27
期刊：
影响因子：
6.2
通讯作者：
IMAMURA, M
中科院分区：
文献类型：
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作者：
ARII, S;MONDEN, K;IMAMURA, M
本研究旨在探讨库普弗细胞在冷藏肝移植物再灌注损伤发展中的可能参与。 In the cold preservation of Kupffer cells with Euro-Collins solution, the proportion of asialo-GM1-positive cells was significantly increased at 12 and 24 hr of storage, and the TNF alpha-producing activity in these cells was approximately fivefold greater than control. Northern印迹分析表明，在冷保存的肝脏再灌注中，TNF α mRNA 显着升高，而预再灌注移植物的 TNF α mRNA 仅轻微诱导。冷藏肝移植物的再灌注实验表明，在灌注液中添加抗TNFα抗体可显着抑制流出液中GOT和LDH水平的升高，并且用库普弗细胞抑制剂氯化钆预处理几乎完全抑制流出液中这些酶的增加。组织学研究显示，在再灌注肝移植物中，血窦和中央静脉中广泛沉积有纤维蛋白样物质，而在钆预处理的肝脏中未观察到明显的沉积。因此，本研究表明，库普弗细胞通过用欧洲柯林斯溶液冷保存引发，然后在再灌注完成时激活。冷保存/再灌注诱导的库普弗细胞活化似乎在伴有窦性微循环障碍的再灌注损伤中起主要作用，并且TNFα是再灌注肝移植物损伤的原因。
The present study was designed to investigate the possible participation of Kupffer cells in the development of reperfusion injury of the cold-stored liver graft. In the cold preservation of Kupffer cells with Euro-Collins solution, the proportion of asialo-GM1-positive cells was significantly increased at 12 and 24 hr of storage, and the TNF alpha-producing activity in these cells was approximately fivefold greater than control. Northern blot analysis demonstrated that TNF alpha mRNA was remarkably elevated in the reperfusion of the cold-preserved liver, although that of the prereperfused graft was only slightly induced. The reperfusion experiments of the cold-stored liver graft showed that addition of anti-TNF alpha antibody to the perfusate suppressed the elevation of the effluent levels of GOT and LDH significantly, and that pretreatment with a Kupffer cell inhibitor, gadolinium chloride, inhibited the increase of these enzymes in the effluents almost completely. Histological study revealed deposition of a fibrinlike substance in the sinusoid and the central veins extensively in the reperfused liver graft, whereas no apparent deposition was observed in the gadolinium-pretreated liver.Thus, the present study showed that Kupffer cells were primed by cold preservation with Euro-Collins solution, and then activated when the reperfusion was done. It seems likely that the Kupffer cell activation induced by cold preservation/reperfusion plays a major role in reperfusion injury with sinusoidal micro circulatory disturbance, and that TNF alpha is responsible for the impairment of the reperfused liver graft.