Exacerbation of acetaminophen-induced disturbances of liver sinusoidal endothelial cells in the absence of Kupffer cells in mice
Exacerbation of acetaminophen-induced disturbances of liver sinusoidal endothelial cells in the absence of Kupffer cells in mice
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DOI：
10.1016/j.toxlet.2010.01.020
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发表时间：
2010-04-15
影响因子：
3.5
通讯作者：
Ju, Cynthia
中科院分区：
文献类型：
--
作者：
Holt, Michael P.;Yin, Hao;Ju, Cynthia
虽然已经有相当多的研究，在肝窦内皮细胞（LSECs）和肝驻留巨噬细胞（枯否细胞，KCs）在对乙酰氨基酚（APAP）诱导的肝损伤的整体发病机制，他们的潜在的相互作用和关系知之甚少。在本研究中，采用脂质体/氯膦酸盐消耗KCs，我们能够证实先前证明的KCs的肝保护作用。这种保护作用可以部分地通过调节LSEC稳态和完整性来介导。进一步加重APAP诱导的LSEC紊乱后，消耗KC与肝血管通透性增加和红细胞蓄积。在APAP攻击之前KCs的消耗也导致LSEC上细胞粘附分子的表达增加。肝内皮细胞的这种增加的紊乱可能是在没有KCs的情况下APAP诱导的肝损伤加重的一个促成因素。然而，这些紊乱也可能是肝损伤增加的结果，因此，不排除在APAP诱导的肝毒性发病过程中KC介导的肝保护的其他机制的可能性。出版社：Elsevier爱尔兰Ltd.
Although there has been considerable research in terms of liver sinusoidal endothelial cells (LSECs) and hepatic resident macrophages (Kupffer cells, KCs) during the overall pathogenesis of acetaminophen (APAP)-induced liver injury, little is known about their potential interaction and relationship. In the present study, employing the use of liposome/clodronate to deplete KCs, we were able to confirm the previously demonstrated hepato-protective role for KCs. Such a protective role may be mediated, in part, via regulation of LSEC homeostasis and integrity. The further aggravation of APAP-induced LSEC disturbance upon depletion of KCs correlated with increased hepatic vascular permeability and red blood cell accumulation. The depletion of KCs prior to APAP challenge also resulted in the increased expression of cellular adhesion molecules on LSECs. Such increased disturbance in the hepatic endothelial may represent a contributing factor in the exacerbation of APAP-induced liver injury in the absence of KCs. However, these disturbances may also be a result of the increased hepatic damage, and as such, does not rule out the potential for additional mechanisms of KC-mediated hepato-protection during the pathogenesis of APAP-induced hepatotoxicity. Published by Elsevier Ireland Ltd.