Bone marrow and non-bone marrow TLR4 regulates hepatic ischemia/reperfusion injury
Bone marrow and non-bone marrow TLR4 regulates hepatic ischemia/reperfusion injury
复制标题
骨髓和非骨髓TLR4调节肝缺血/再灌注损伤
DOI：
10.1016/j.bbrc.2009.08.149
复制
发表时间：
2009-11-13
影响因子：
3.1
通讯作者：
Zheng Qichang
中科院分区：
文献类型：
--
作者：
Wang Hui;Zhang Jinxiang;Zheng Qichang
肝脏缺血再灌注损伤（IRI）是一个高度协调的过程，经常在肝移植，肝脏手术和失血性休克中观察到。Toll样受体4（TLR 4）广泛表达于各种肝细胞，通过TLR 4信号转导在IRI的发病机制中起关键作用。尽管已经广泛研究了在肝的非实质细胞（NPC）（包括枯否细胞和中性粒细胞）上表达的TLR 4在IRI中的作用，但是在IRI过程中肝窦内皮细胞（LSEC）或肝细胞上的TLR 4信号传导，以及它们在再灌注后期与骨髓来源的TLR 4的协调，在很大程度上是未知的。我们产生了接受肝脏IRI的TLR 4嵌合小鼠，并检查了肝损伤的程度和损伤的潜在机制。结果表明，骨髓或非骨髓来源的TLR 4突变可通过细胞因子释放和中性粒细胞浸润降低再灌注后期肝脏IRI，而非骨髓来源的TLR 4可调节肝细胞和LSEC上ICAM-1的表达，加重其损伤。因此，在肝脏IRI的发生过程中，骨髓源性和非骨髓源性细胞上的TLR 4均是必需的。(C)2009 Elsevier Inc. All rights reserved.
Hepatic ischemia-reperfusion injury (IRI) is a highly coordinated process often observed during liver transplantation, liver surgery, and hemorrhagic shock. Signaling through toll-like receptor 4 (TLR4), which is widely expressed on all kinds of liver cells, appears critical in the pathogenesis of IRI. Although the role of TLR4 expressed on non-parenchymal cells (NPCs) of the liver, including Kupffer cells and neutrophils, in IRI has been widely studied, TLR4 signaling on liver sinusoidal endothelial cells (LSECs) or hepatocytes in the process of IRI, and their coordination with bone marrow derived TLR4 in the late reperfusion stage, is largely unknown. We produced TLR4 chimeric mice that received hepatic IRI, and examined the degree of liver injury and the underlying mechanisms of injury. Results indicated that mutation of TLR4 on bone-marrow or non-bone marrow derived cells reduced hepatic IRI in the late reperfusion stage via cytokine release and neutrophil infiltration, while non-bone marrow derived TLR4 regulated the expression of ICAM-1 on hepatocytes and LSECs, exacerbating their injury. In conclusion, both TLR4 on bone marrow derived and non-bone marrow derived cells were necessary in the process of hepatic IRI. (C) 2009 Elsevier Inc. All rights reserved.