PDF(Pubmed)
Abstract：
Lipopolysaccharide-induced (LPS) inflammation is used as model to understand the role of inflammation in brain diseases. However, no studies have assessed the ability of peripheral low-level chronic LPS to induce neutrophil activation in the periphery and brain. Subclinical levels of LPS were injected intraperitoneally into mice to investigate its impacts on neutrophil frequency and activation. Neutrophil activation, as measured by CD11b expression, was higher in LPS-injected mice compared to saline-injected mice after 4 weeks but not 8 weeks of injections. Neutrophil frequency and activation increased in the periphery 4-12 h and 4-8 h after the fourth and final injection, respectively. Increased levels of G-CSF, TNFa, IL-6, and CXCL2 were observed in the plasma along with increased neutrophil elastase, a marker of neutrophil extracellular traps, peaking 4 h following the final injection. Neutrophil activation was increased in the brain of LPS-injected mice when compared to saline-injected mice 4-8 h after the final injection. These results indicate that subclinical levels of peripheral LPS induces neutrophil activation in the periphery and brain. This model of chronic low-level systemic inflammation could be used to understand how neutrophils may act as mediators of the periphery-brain axis of inflammation with age and/or in mouse models of neurodegenerative or neuroinflammatory disease.
摘要：
脂多糖诱导的（LPS）炎症被用作模型，以了解炎症在脑疾病中的作用。然而,尚无研究评估外周低水平慢性LPS诱导外周和大脑中性粒细胞活化的能力.将亚临床水平的LPS腹膜内注射入小鼠以研究其对中性粒细胞频率和活化的影响。中性粒细胞激活，通过CD11b表达来衡量，与注射生理盐水的小鼠相比，注射LPS的小鼠在注射4周后而不是8周后更高。在第四次和最后一次注射后4-12小时和4-8小时，外周中性粒细胞频率和激活增加，分别。G-CSF水平升高,TNFa,在血浆中观察到IL-6和CXCL2，同时中性粒细胞弹性蛋白酶增加，嗜中性粒细胞胞外陷阱的标志，最终注射后4小时达到峰值。最终注射后4-8小时，与注射盐水的小鼠相比，注射LPS的小鼠的大脑中的中性粒细胞活化增加。这些结果表明外周LPS的亚临床水平诱导外周和脑中的嗜中性粒细胞活化。这种慢性低水平全身性炎症的模型可用于了解嗜中性粒细胞如何随着年龄和/或在神经退行性或神经炎性疾病的小鼠模型中充当炎症的外周-脑轴的介质。
