Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock
Halobacterial nano vesicles displaying murine bactericidal permeability-increasing protein rescue mice from lethal endotoxic shock
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DOI：
10.1038/srep33679
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发表时间：
2016-09-20
影响因子：
4.6
通讯作者：
Chakravortty, Dipshikha
中科院分区：
文献类型：
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作者：
Balakrishnan, Arjun;DasSarma, Priya;Chakravortty, Dipshikha
杀菌/通透性增加蛋白（BPI）通过与革兰氏阴性菌的LPS相互作用而具有抗炎和中和内毒素的活性。目前的研究探讨了使用小鼠BPI（mBPI）表达嗜盐微囊泡纳米颗粒（GVNPs）治疗高危患者内毒素血症的可行性，使用D-半乳糖胺诱导的内毒素休克的小鼠模型。使用盐杆菌NRC-1表达融合到GVNP GvpC蛋白的mBPI的N-末端199个氨基酸残基，并结合到盐古菌GVNP的表面。我们的结果表明，mBPIN-GVNPs的递送增加了用致死浓度的脂多糖（LPS）和D-半乳糖胺攻击的小鼠的存活率。此外，mBPIN-GVNP处理的小鼠显示出炎症症状减轻，包括炎性贫血、嗜中性粒细胞募集、肝细胞凋亡以及促炎血清细胞因子水平增加。
Bactericidal/permeability-increasing protein (BPI) had been shown to possess anti-inflammatory and endotoxin neutralizing activity by interacting with LPS of Gram-negative bacteria. The current study examines the feasibility of using murine BPI (mBPI) expressed on halophilic Archaeal gas vesicle nanoparticles (GVNPs) for the treatment of endotoxemia in high-risk patients, using a murine model of D-galactosamine-induced endotoxic shock. Halobacterium sp. NRC-1 was used to express the N-terminal 199 amino acid residues of mBPI fused to the GVNP GvpC protein, and bound to the surface of the haloarchaeal GVNPs. Our results indicate that delivery of mBPIN-GVNPs increase the survival rate of mice challenged with lethal concentrations of lipopolysaccharide (LPS) and D-galactosamine. Additionally, the mBPIN-GVNP-treated mice displayed reduced symptoms of inflammation, including inflammatory anemia, recruitment of neutrophils, liver apoptosis as well as increased pro-inflammatory serum cytokine levels.