Murine Kupffer cells are protective in total hepatic ischemia/reperfusion injury with bowel congestion through IL-10.
Murine Kupffer cells are protective in total hepatic ischemia/reperfusion injury with bowel congestion through IL-10.
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DOI：
10.4049/jimmunol.0902024
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发表时间：
2010-05-15
期刊：
影响因子：
--
通讯作者：
Chavin KD
中科院分区：
文献类型：
--
作者：
Ellett JD;Atkinson C;Evans ZP;Amani Z;Balish E;Schmidt MG;van Rooijen N;Schnellmann RG;Chavin KD
枯否细胞(Kupffer cell，KCs)被认为是通过在应激反应中产生促炎细胞因子和活性氧来介导肝细胞损伤的。在这项研究中，我们从肝脏中去除KCs，以检测它们在伴有肠道充血的全肝热缺血/再灌注(I/R)损伤中的作用。8周龄C57BL/10J小鼠在肝脏缺血35min肠淤血前48h注射脂质体氯屈膦酸盐，再灌注6h或24h。KC耗竭的动物比稀释剂处理的动物死亡率更高，转氨酶水平增加了10倍，这与小叶中心坏死的增加有关。内毒素与内皮细胞有广泛的结合，这与KC耗竭组与稀释剂处理组的内皮细胞黏附分子上调有关。在KC耗竭的动物中，促炎细胞因子水平增加，IL-10水平随之降低。当KC耗竭小鼠接受重组IL-10治疗时，它们对I/R的肝损伤与稀释剂处理的小鼠相似，内皮细胞黏附分子和促炎细胞因子水平降低。在全I/R伴随肠道充血的情况下，KCs在肝脏中具有保护作用，并且并不像之前认为的那样有害。这种保护似乎是由于KC分泌了强大的抗炎细胞因子IL-10。
Kupffer cells (KCs) are thought to mediate hepatocyte injury via their production of proinflammatory cytokines and reactive oxygen species in response to stress. In this study, we depleted KCs from the liver to examine their role in total warm hepatic ischemia/reperfusion (I/R) injury with bowel congestion. We injected 8-wk-old C57BL/10J mice with liposome-encapsulated clodronate 48 h before 35 min of hepatic ischemia with bowel congestion, followed by 6 or 24 h of reperfusion. KC-depleted animals had a higher mortality rate than diluent-treated animals and a 10-fold elevation in transaminase levels that correlated with increases in centrilobular necrosis. There was extensive LPS binding to the endothelial cells, which correlated with an upregulation of endothelial adhesion molecules in the KC-depleted animals versus diluent-treated animals. There was an increase in the levels of proinflammatory cytokines in KC-depleted animals, and a concomitant decrease in IL-10 levels. When KC-depleted mice were treated with recombinant IL-10, their liver damage profile in response to I/R was similar to diluent-treated animals, and endothelial cell adhesion molecules and proinflammatory cytokine levels decreased. KCs are protective in the liver subjected to total I/R with associated bowel congestion and are not deleterious as previously thought. This protection appears to be due to KC secretion of the potent anti-inflammatory cytokine IL-10.
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