Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Liver Sinusoidal Endothelial Cells via High-Density Lipoprotein.
Blood-Borne Lipopolysaccharide Is Rapidly Eliminated by Liver Sinusoidal Endothelial Cells via High-Density Lipoprotein.
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DOI：
10.4049/jimmunol.1600702
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发表时间：
2016-09-15
期刊：
影响因子：
--
通讯作者：
Ganesan LP
中科院分区：
文献类型：
--
作者：
Yao Z;Mates JM;Cheplowitz AM;Hammer LP;Maiseyeu A;Phillips GS;Wewers MD;Rajaram MV;Robinson JM;Anderson CL;Ganesan LP
在革兰氏阴性细菌感染期间，过量的脂多糖（LPS）通过对免疫细胞的作用诱导炎症和脓毒症。然而，大部分LPS可以通过肝脏从循环中清除。肝脏清除被认为是一个缓慢的过程，完全由吞噬驻留巨噬细胞，枯否细胞（KC）介导。然而，我们发现LPS从循环中迅速消失，在小鼠中的半衰期为2-4分钟，肝脏从血液循环中消除约四分之三的LPS。使用显微镜技术，我们发现肝脏中约75%的荧光标记的LPS与肝窦内皮细胞（LSEC）相关，仅约25%与KC相关。值得注意的是，LSEC-KC相关LPS的比率在输注后45分钟保持不变，表明LSEC独立地处理LPS。最有趣的是，LPS生物活性的动力学分析的结果，使用修改的鲎变形细胞裂解物测定，表明重组因子-C，LPS结合蛋白，竞争性抑制HDL介导的LPS协会与LSEC的早期过程。输注后3分钟，75%的输注的荧光标记的LPS-HDL复合物与LSEC缔合，表明HDL促进LPS清除，这支持了先前的观点。这些结果使我们提出了一种新的LSEC和HDL清除LPS的范例，具有避免脓毒症期间炎症的潜力。
During Gram-negative bacterial infections, excessive lipopolysaccharide (LPS) induces inflammation and sepsis via action on immune cells. However, the bulk of LPS can be cleared from circulation by the liver. Liver clearance is thought to be a slow process mediated exclusively by phagocytic resident macrophages, Kupffer cells (KC). However, we discovered that LPS disappears rapidly from the circulation, with a half-life of 2–4 minutes in mice and liver eliminates about three quarters of LPS from blood circulation. Using microscopic techniques, we found that ~75% of fluor-tagged LPS in liver became associated with liver sinusoidal endothelial cells (LSEC) and only ~25% with KC. Notably, the ratio of LSEC-KC associated LPS remained unchanged 45 min after infusion, indicating that LSEC independently processes the LPS. Most interestingly, results of kinetic analysis of LPS bioactivity, using modified limulus amebocyte lysate assay, suggest that recombinant factor-C, an LPS binding protein, competitively inhibits HDL-mediated LPS association with LSEC early in the process. Supporting the previous notion 3 min post-infusion, 75% of infused fluorescently-tagged LPS-HDL complex associates with LSEC, suggesting that HDL facilitates LPS clearance. These results lead us to propose a new paradigm of LSEC and HDL in clearing LPS with a potential to avoid inflammation during sepsis.
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影响因子：
3.4
作者：
Kubiak, Jakubs;Brewer, Jonathan;Bagatolli, Luis A.
通讯作者：
Bagatolli, Luis A.
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：
3.1
作者：
FLEGEL, WA;WOLPL, A;NORTHOFF, H
通讯作者：
NORTHOFF, H
通过肝正弦内皮对血传播病毒的快速有效清除。
影响因子：
6.7
作者：
Ganesan LP;Mohanty S;Kim J;Clark KR;Robinson JM;Anderson CL
通讯作者：
Anderson CL
DOI：
10.1128/cdli.12.1.60-67.2005
发表时间：
2005-01-01
期刊：
CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY
影响因子：
--
作者：
Copeland, S;Warren, HS;Remick, D
通讯作者：
Remick, D