Cutrín J C, Llesuy S, Boveris A
Department of Experimental Medicine and Oncology, University of Torino, Italy.
Cell Biochem Funct. 1998 Mar;16(1):65-72. doi: 10.1002/(SICI)1099-0844(199803)16:1<65::AID-CBF772>3.0.CO;2-U.
It has been reported that hepatocyte metabolism and function can be modulated by the activated Kupffer cell through the release of different biomolecules like cytokines, eicosanoids, oxygen free radicals and enzymes. In relation to these paracrine factors involved in circuits of intercellular communication, the existence of a hepatic oxygen sensor located in the Kupffer cell has been postulated. According to this postulate the oxygen metabolism of the liver parenchymal cells could be under the control of the Kupffer cells. In order to study the role of the Kupffer cell in the reperfusion syndrome of the liver, a lobular ischaemia-reperfusion model was performed in rats with or without previous treatment with gadolinium chloride to block Kupffer cell function. Spontaneous chemiluminescence of the liver surface, oxygen uptake by tissue slices and tertbutyl hydroperoxide-initiated chemiluminescence determinations were performed to evaluate the oxygen metabolism and the oxy-radical generation by the liver. The lower basal photoemission, in parallel with a lower basal oxygen uptake registered in the hepatic lobes from the animals pretreated with gadolinium chloride clearly indicates that the gadolinium chloride-dependent functional inhibition of Kupffer cell leads to a downregulation of oxygen metabolism by the liver. Moreover, the intensity of oxidative stress exhibited by the postischaemic lobes appears to be closely linked with the Kupffer cell activity. On the basis of the data obtained we propose that a paracrine circuit between activated Kupffer cell and hepatocytes is an early key event in the induction of postischaemic oxidative stress in the liver. Furthermore the interference with the mitochondrial electron flow by some biomolecules released from the activated Kupffer cell, such as tumour necrosis factor, interleukins, eicosanoids, etc., would increase the rate of generation of reactive oxygen species by the inhibited mitochondrial respiratory chain.
据报道，活化的库普弗细胞可通过释放细胞因子、类二十烷酸、氧自由基和酶等不同生物分子来调节肝细胞的代谢和功能。关于这些参与细胞间通讯回路的旁分泌因子，有人推测在库普弗细胞中存在一种肝脏氧传感器。根据这一推测，肝实质细胞的氧代谢可能受库普弗细胞的控制。为了研究库普弗细胞在肝脏再灌注综合征中的作用，在大鼠身上建立了小叶缺血-再灌注模型，这些大鼠在使用或未使用氯化钆预处理以阻断库普弗细胞功能的情况下进行实验。通过测定肝脏表面的自发化学发光、组织切片的氧摄取以及叔丁基过氧化氢引发的化学发光，来评估肝脏的氧代谢和氧自由基生成情况。在用氯化钆预处理的动物肝脏叶中，较低的基础光发射与较低的基础氧摄取同时出现，这清楚地表明氯化钆对库普弗细胞的功能抑制导致肝脏氧代谢下调。此外，缺血后叶所表现出的氧化应激强度似乎与库普弗细胞活性密切相关。根据所获得的数据，我们提出活化的库普弗细胞与肝细胞之间的旁分泌回路是肝脏缺血后氧化应激诱导过程中的一个早期关键事件。此外，活化的库普弗细胞释放的一些生物分子，如肿瘤坏死因子、白细胞介素、类二十烷酸等，对线粒体电子流的干扰，会增加受抑制的线粒体呼吸链产生活性氧的速率。
