Toll-like receptor 4 knockout mice are protected from endothelial overactivation in the absence of Kupffer cells after total hepatic ischemia/reperfusion.
Toll-like receptor 4 knockout mice are protected from endothelial overactivation in the absence of Kupffer cells after total hepatic ischemia/reperfusion.
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DOI：
10.1002/lt.22333
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发表时间：
2011-09
影响因子：
4.6
通讯作者：
Chavin, Kenneth D.
中科院分区：
文献类型：
--
作者：
Ellett, Justin D.;Atkinson, Carl;Evans, Zachary P.;Amani, Zainab;Balish, Edward;Schmidt, Michael G.;Schnellmann, Rick G.;Chavin, Kenneth D.
库普弗细胞（KC）是小鼠肝脏I/R损伤的重要介质。利用脂质体氯膦酸盐（LC）的管理，我们已经表明，KC是保护模型的全肝缺血与肠充血。在这里，我们调查的作用，TLR 4在损伤后发生的I/R在KC耗尽的肝脏。我们给8周龄的C57 BL/10 J或C57 BL/10 ScN（TLR 4KO）小鼠注射脂质体包封的氯膦酸盐48小时，然后进行35分钟的热肝缺血伴肠充血，随后进行6小时或24小时的再灌注。KC耗竭的动物死亡率增加，转氨酶水平增加10倍，与小叶中心坏死增加相关。这些变化在TLR 4KO动物中不存在。I/R后LPS广泛结合内皮细胞，并且这种结合在TLR 4KO动物中减少。同时，在LC处理的动物中存在TLR 4KO动物中不存在的内皮细胞粘附分子的上调。最后，在LC处理的动物中促炎细胞因子水平显著增加，并且TLR 4KO动物受到保护以抵抗这种增加。总之，TLR 4促进内皮细胞过度活化后I/R在KC的情况下。
Kupffer cells (KC) have been shown to be critical mediators of I/R injury in the murine liver. Utilizing liposomal clodronate (LC) administration, we have shown that KC are protective in models of total hepatic ischemia with bowel congestion. Here, we investigate the role of TLR4 in the damage that occurs after I/R in KC-depleted livers. We injected 8-week old C57BL/10J or C57BL/10ScN (TLR4KO) mice with liposome-encapsulated clodronate 48 hours prior to 35 minutes of warm hepatic ischemia with bowel congestion, followed by either 6 or 24 hours of reperfusion. KC depleted animals had increased mortality as well as a 10-fold increase in transaminase levels that correlated with increases in centrilobular necrosis. These changes were absent in TLR4KO animals. LPS bound extensively to endothelial cells after I/R, and this binding was diminished in TLR4KO animals. In conjunction, there was an upregulation of endothelial cell adhesion molecules in LC-treated animals that was absent in TLR4KO animals. Finally, there was a dramatic increase in proinflammatory cytokine levels in LC-treated animals, and TLR4KO animals were protected against this increase. In conclusion, TLR4 promotes endothelial overactivation after I/R in the absence of KC.
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影响因子：
1.9
作者：
OHIRA, H;UENO, T;KASUKAWA, R
通讯作者：
KASUKAWA, R
DOI：
10.4049/jimmunol.0902024
发表时间：
2010-05-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ellett JD;Atkinson C;Evans ZP;Amani Z;Balish E;Schmidt MG;van Rooijen N;Schnellmann RG;Chavin KD
通讯作者：
Chavin KD
影响因子：
4.4
作者：
Izuishi, Kunihiko;Tsung, Allan;Billiar, Timothy R.
通讯作者：
Billiar, Timothy R.
影响因子：
4
作者：
Granado, M;Martin, AI;López-Calderón, A
通讯作者：
López-Calderón, A
影响因子：
3.6
作者：
Chen, Li C.;Gordon, Ronald E.;Laskin, Debra L.
通讯作者：
Laskin, Debra L.