Lipopolysaccharidebinding protein -(LBP) blockade augments the protective effect of granulocyte colony-stimulating factor (G-CSF) in a rat sepsis model.
Lipopolysaccharidebinding protein -(LBP) blockade augments the protective effect of granulocyte colony-stimulating factor (G-CSF) in a rat sepsis model.
复制标题
脂多糖结合蛋白 (LBP) 阻断可增强粒细胞集落刺激因子 (G-CSF) 在大鼠脓毒症模型中的保护作用。
DOI：
10.1097/shk.0000000000000338
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发表时间：
2015
期刊：
影响因子：
3.1
通讯作者：
Dahmen Uta
中科院分区：
文献类型：
--
作者：
Liu Anding;Weiss Stefanie;Fang Haoshu;Claus Ralf A;Rodel Jurgen;Dirsch Olaf;Dahmen Uta
粒细胞集落刺激因子（G-CSF）对脓毒症的作用在临床研究中存在争议。我们以前证明，G-CSF治疗诱导脂多糖（LPS）敏化通过上调LPS结合蛋白（LBP）。我们推测，G-CSF治疗脓毒症的无效作用可能是由于其上调LBP的能力。因此，阻断LBP可以减弱G-CSF诱导的LPS致敏作用，保护动物免受多微生物脓毒症的侵害。用G-CSF预处理可上调内源性LBP水平，并通过给予特异性阻断肽LBPK 95 A阻断LBP蛋白。腹腔注射粪浆诱导多菌性脓毒症。每3小时监测一次大鼠，直至72小时，以观察存活率。组织损伤，细菌浸润，局部炎症反应，并在0，2，和12小时后，脓毒症的侮辱中性粒细胞浸润进行了分析。当与LBPK 95 A治疗组合时，G-CSF预处理的生存益处得到改善（对照组vs. G-CSF vs. combi：36% vs. 56% vs. 93%; P< 0.05）。G-CSF和LBPK 95 A的联合治疗与最小的组织损伤相关。用LBPK 95 A处理显著抑制中性粒细胞浸润而不干扰细菌清除。LBPK 95 A可抑制G-CSF诱导的炎症致敏作用，表现为细胞因子表达减少，核因子κ B和信号转导与转录激活因子3信号通路激活。总之，这些结果表明，通过G-CSF预处理预防性增强宿主反应的效果通过抑制LBP的上调而进一步增强。华中科技大学同济医学院同济医院实验医学中心，中国武汉;德国耶拿耶拿大学医院普外科、内脏和血管外科实验移植外科;安徽医科大学病理生理学系，中国合肥; §综合研究和治疗中心，脓毒症控制和护理中心（CSCC），耶拿大学医院，耶拿，德国;耶拿大学医院医学微生物学研究所，耶拿，德国;和德国耶拿耶拿大学医院病理学研究所
The effect of granulocyte colony-stimulating factor (G-CSF) on sepsis is discussed controversially in clinical studies. We previously demonstrated that G-CSF treatment induced lipopolysaccharide (LPS) sensitization via up-regulation of LPS-binding protein (LBP). We hypothesized that the futile effect of G-CSF-treatment in sepsis might be due to its ability to up-regulate LBP. Therefore, blockade of LBP may attenuate the G-CSF–induced LPS sensitization and protect animals from polymicrobial sepsis. Endogenous LBP levels were up-regulated by pretreatment with G-CSF, and the LBP protein was blocked by administration of a specific blocking peptide—LBPK95A. Polymicrobial sepsis was induced by intraperitoneal injection of feces slurry. Rats were monitored every 3 up to 72 h to observe the survival rate. Tissue injury, bacterial infiltration, local inflammatory response, and neutrophil infiltration at 0, 2, and 12 h after the septic insult were analyzed. The survival benefit of G-CSF pretreatment was improved when combined with LBPK95A treatment (control vs. G-CSF vs. combi: 36% vs. 56% vs. 93%; P< 0.05). Combined treatment of G-CSF and LBPK95A was associated with the minimal tissue damage. Treatment with LBPK95A significantly inhibited the neutrophil infiltration without interfering with the bacterial clearance. The G-CSF–induced inflammatory sensitization effect was inhibited by LBPK95A, indicated by the decrease of cytokines expression, and the activation of nuclear factor kappa B and signal transducer and activator of transcription 3 signaling pathway. In conclusion, these results suggested that the effect of prophylactic augmentation of the host’s response via G-CSF pretreatment was further enhanced by inhibition of the up-regulation of LBP.* Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;† Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena, Germany;‡ Department of Pathophysiology, Anhui Medical University, Hefei, China; § Integrated Research and Treatment Center, Center for Sepsis Control and Care (CSCC), Jena University Hospital, Jena, Germany;∥ Institute of Medical Microbiology, Jena University Hospital, Jena, Germany; and¶ Institute for Pathology, Jena University Hospital, Jena, Germany