Hepatic uptake and deacylation of the LPS in bloodborne LPS-lipoprotein complexes.
Hepatic uptake and deacylation of the LPS in bloodborne LPS-lipoprotein complexes.
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DOI：
10.1177/1753425912442431
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发表时间：
2012-12
期刊：
影响因子：
3.2
通讯作者：
Varley AW
中科院分区：
文献类型：
--
作者：
Shao B;Munford RS;Kitchens R;Varley AW
许多证据表明，细菌脂多糖（LPS，内毒素）主要通过肝脏从血液中清除，但肝脏摄取机制仍不确定和有争议。在血浆中，LPS可以是“游离的”（作为聚集体、细菌膜片段或松散地结合到白蛋白、CD 14或其他蛋白质）或“结合的”（与脂蛋白复合）。尽管大多数游离LPS被枯否细胞吸收，但脂蛋白结合的LPS似乎主要由肝细胞清除。在这里，我们比较了肝脏的能力，采取和脱酰化游离LPS聚集体和LPS在预先形成的LPS-HDL（高密度脂蛋白）复合物。将少量荧光（FITC-）LPS注射到侧尾静脉后1小时至7天检查小鼠，我们发现FITC-LPS几乎完全在枯否细胞内或邻近枯否细胞。正如预期的那样，与HDL复合的FITC-LPS（FITC-LPS-HDL）从循环中消失得更慢，并且在肝脏中发现注射剂量的FITC-LPS的较小部分。出乎意料的是，作为FITC-LPS-HDL复合物注射的FITC-LPS也发现于窦状隙内、枯否细胞附近或枯否细胞内。在其他实验中，我们发现游离和HDL结合的放射性标记的LPS都通过酰氧酰基水解酶（AOAH）进行酶促脱酰，AOAH是主要由枯否细胞在肝脏内产生的LPS失活酶。我们的观察结果表明，枯否细胞和AOAH在清除和代谢游离LPS和循环LPS-HDL复合物中的LPS中起重要作用。
Much evidence indicates that bacterial lipopolysaccharide (LPS, endotoxin) is removed from the bloodstream mainly by the liver, yet the hepatic uptake mechanisms remain uncertain and controversial. In plasma, LPS can be either “free” (as aggregates, bacterial membrane fragments, or loosely bound to albumin, CD14, or other proteins) or “bound” (complexed with lipoproteins). Whereas most free LPS is taken up by Kupffer cells, lipoprotein-bound LPS has seemed to be cleared principally by hepatocytes. Here we compared the liver’s ability to take up and deacylate free LPS aggregates and the LPS in preformed LPS-HDL (high density lipoprotein) complexes. In mice examined from 1 hour to 7 days after a small amount of fluorescent (FITC-)LPS was injected into a lateral tail vein, we found FITC-LPS almost entirely within, or adjacent to, Kupffer cells. As expected, FITC-LPS complexed with HDL (FITC-LPS-HDL) disappeared more slowly from the circulation and a smaller fraction of the injected dose of FITC-LPS was found in the liver. Unexpectedly, the FITC-LPS injected as FITC-LPS-HDL complexes was also found within sinusoids, adjacent to or within Kupffer cells. In other experiments, we found that both free and HDL-bound radiolabeled LPS underwent enzymatic deacylation by acyloxyacyl hydrolase (AOAH), the LPS-inactivating enzyme that is principally produced within the liver by Kupffer cells. Our observations suggest that Kupffer cells and AOAH play important roles in clearing and catabolizing both free LPS and the LPS in circulating LPS-HDL complexes.
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影响因子：
--
作者：
Munford, Robert;Lu, Mingfang;Varley, Alan
通讯作者：
Varley, Alan
影响因子：
6.5
作者：
Kitchens, RL;Thompson, PA;O'Keefe, GE
通讯作者：
O'Keefe, GE
影响因子：
4.8
作者：
Kitchens, RL;Wolfbauer, G;Munford, RS
通讯作者：
Munford, RS
DOI：
10.1111/j.1530-0277.2010.01399.x
发表时间：
2011-05
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Miller AM;Horiguchi N;Jeong WI;Radaeva S;Gao B
通讯作者：
Gao B
影响因子：
6.4
作者：
Ge, YM;Ezzell, RM;Warren, HS
通讯作者：
Warren, HS