Effects of Pulmonary Exposure to Carbon Nanotubes on Lung and Systemic Inflammation with Coagulatory Disturbance Induced by Lipopolysaccharide in Mice
Effects of Pulmonary Exposure to Carbon Nanotubes on Lung and Systemic Inflammation with Coagulatory Disturbance Induced by Lipopolysaccharide in Mice
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DOI：
10.3181/0805-rm-179
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发表时间：
2008-12-01
影响因子：
3.2
通讯作者：
Shimada, Akinori
中科院分区：
文献类型：
--
作者：
Inoue, Ken-ichiro;Takano, Hirohisa;Shimada, Akinori
尽管对脂多糖（LPS）相关炎症伴凝血障碍的发病机制进行了深入研究，但其加重因素尚未得到很好的探讨。本研究检测了肺部暴露于两种类型的纳米材料（碳纳米管：CNT [单壁：SWCNT，和多壁：MWCNT]）对肺部炎症和随后的全身炎症的影响，以及肺部暴露于LPS诱导的小鼠凝血障碍及其体外细胞机制。将ICR雄性小鼠分成6个实验组，分别在肠道内接受载体、两种类型的CNT（4 mg/kg）、LPS（33 μ g/kg）或LPS加任一类型的CNT。治疗后24小时，两种类型的CNT单独诱导肺部炎症，增强肺部促炎细胞因子的表达，但没有协同加重LIPS引起的肺部炎症。单壁碳纳米管显着诱导/增强肺通透性和高纤维蛋白原血症，并减少活化蛋白C的存在或不存在的LPS，而多壁碳纳米管适度。两种CNT都适度但不显著地升高了促炎细胞因子和趋化因子的循环水平。在LPS的存在下，CNT倾向于升高介质的水平，总体趋势，这是更突出的单壁CNT比多壁CNT。体外研究表明，两种CNT都能扩增LPS诱导的外周血单核细胞细胞因子的产生。这些结果表明，CNT可以促进全身炎症与凝血障碍，至少部分，通过单核细胞的激活，这是伴随着中度增强急性肺部炎症相关的LIPS。Exp Biol Med 233：1583-1590. 2008
Despite intensive research as to the pathogenesis of lipopolysaccharide (LPS)-related inflammation with coagulatory disturbance, their exacerbating factors have not been well explored. This study examined the effects of pulmonary exposure to two types of nano-sized materials (carbon nanotubes: CNT [single-wall: SWCNT, and multi-wall: MWCNT]) on lung inflammation and consequent systemic inflammation with coagulatory disturbance induced by pulmonary exposure to LPS in mice and their cellular mechanisms in vitro. ICR male mice were divided into 6 experimental groups that intratracheally received the vehicle, two types of CNT (4 mg/kg), LPS (33 mu g/kg), or LPS plus either type of CNT. Twenty-four hours after treatment, both types of CNT alone induced lung inflammation with enhanced lung expression of proinflammatory cytokines, but did not synergistically exacerbate lung inflammation elicited by LIPS. SWCNT significantly induced/enhanced pulmonary permeability and hyperfibrinogenemia and reduced activated protein C in the absence or presence of LPS, whereas MWCNT did moderately. Both CNT moderately, but not significantly, elevated circulatory levels of proinflammatory cytokines and chemokines. In the presence of LPS, CNT tended to elevate the levels of the mediators with an overall trend, which was more prominent with SWCNT than with MWCNT. In vitro study showed that both CNT amplified LPS-induced cytokine production from peripheral blood monocytes. These results suggest that CNT can facilitate systemic inflammation with coagulatory disturbance, at least in part, via the activation of mononuclear cells, which is accompanied by moderate enhancement of acute lung inflammation related to LIPS. Exp Biol Med 233:1583-1590. 2008