Granulocyte colony stimulating factor induces lipopolysaccharide (LPS) sensitization via upregulation of LPS binding protein in rat.
Granulocyte colony stimulating factor induces lipopolysaccharide (LPS) sensitization via upregulation of LPS binding protein in rat.
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粒细胞落刺激因子通过上调大鼠的LPS结合蛋白来诱导脂多糖（LPS）敏化。
DOI：
10.1371/journal.pone.0056654
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Dahmen U
中科院分区：
文献类型：
--
作者：
Fang H;Liu A;Sun J;Kitz A;Dirsch O;Dahmen U
肝脏是清除内毒素的主要器官。在动物模型中，对内毒素的敏感性与内毒素结合蛋白(LBP)的上调有关。因此，我们推测LBP可能通过增加肝脏对内毒素的摄取而诱导内毒素增敏。本研究旨在探讨LBP在脂多糖诱导的全身炎症反应综合征(SIRS)发病机制中的作用。经粒细胞集落刺激(G-CSF)处理后，LBP表达上调。用LBP封闭肽LBPK95A阻断LBP进一步证实了LBP的作用。经G-CSF处理后，骨髓细胞和肝脏中LBP表达上调。G-CSF诱导的LBP上调可引起大鼠的内毒素超敏反应，表现为更高的死亡率和更严重的肝损伤。值得注意的是，LBP阻断提高了存活率，减轻了肝损伤。LBP诱导的内毒素超敏反应与肝脏对内毒素的摄取增加和肝组织Toll样受体(TLR)-4等内毒素受体表达增加有关。此外，LBP还介导了早期中性粒细胞的浸润，导致单核细胞在肝脏中的募集增加。综上所述，G-CSF诱导的LBP表达可作为研究内毒素致敏作用的新模型。我们证实了LBP上调在内毒素诱导的SIRS发病机制中的重要作用。
Liver is the main organ for lipopolysaccharide (LPS) clearance. Sensitization to LPS is associated with the upregulation of LPS-binding protein (LBP) in animal models. Therefore, we hypothesized that LBP could induce LPS sensitization through enhancing hepatic uptake of LPS. In this study, we examined the role of LBP in pathogenesis of LPS induced systemic inflammatory response syndrome (SIRS). LBP expression was upregulated after granulocyte colony stimulating (G-CSF) pretreatment. The effect of LBP was further confirmed by blockade of LBP using LBP blocking peptide – LBPK95A. After G-CSF pretreatment, upregulation of LBP was observed in bone marrow cells and liver. The G-CSF induced LBP upregulation caused LPS hypersensitization in rats as indicated by higher mortality and severer liver damage. Of note, LBP blockade increased the survival rate and attenuated the liver injury. The LBP induced LPS hypersensitization was associated with increased hepatic uptake of LPS and augmented hepatic expression of LPS receptors, such as toll-like receptor (TLR)-4. Furthermore, LBP mediated early neutrophil infiltration, which led to increased monocyte recruitment in liver after LPS administration. In conclusion, G-CSF induced LBP expression could serve as a new model for investigation of LPS sensitization. We demonstrated the crucial role of LBP upregulation in pathogenesis of LPS induced SIRS.
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影响因子：
3.7
作者：
Liu A;Fang H;Dirsch O;Jin H;Dahmen U
通讯作者：
Dahmen U
DOI：
10.1073/pnas.76.11.5939
发表时间：
1979-01-01
影响因子：
11.1
作者：
GALANOS, C;FREUDENBERG, MA;REUTTER, W
通讯作者：
REUTTER, W
DOI：
10.1073/pnas.91.17.7922
发表时间：
1994-08-16
影响因子：
11.1
作者：
GALLAY, P;HEUMANN, D;GLAUSER, MP
通讯作者：
GLAUSER, MP
影响因子：
3.3
作者：
MILESKI, WJ;WINN, RK;RICE, CL
通讯作者：
RICE, CL
影响因子：
6.8
作者：
Schumann, RR;Zweigner, J
通讯作者：
Zweigner, J