Low-dose cisplatin administration to septic mice improves bacterial clearance and programs peritoneal macrophage polarization to M1 phenotype
Low-dose cisplatin administration to septic mice improves bacterial clearance and programs peritoneal macrophage polarization to M1 phenotype
复制标题
对脓毒症小鼠给予低剂量顺铂可改善细菌清除并将腹膜巨噬细胞极化至 M1 表型。
DOI：
10.1111/2049-632x.12189
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发表时间：
2014-11-01
影响因子：
3.3
通讯作者：
Wei, Yuquan
中科院分区：
文献类型：
--
作者：
Li, Yanyan;Wang, Zhenling;Wei, Yuquan
脓毒症是对感染的全身性炎症反应，巨噬细胞的早期反应在控制感染的微生物方面至关重要。我们使用盲肠结扎穿孔（CLP）脓毒症模型来确定顺铂（0.1、0.5和1 mg/kg）对腹腔巨噬细胞、控制腹膜/血液细菌感染和全身炎症的作用。结果发现，腹腔注射低剂量顺铂（0.1和0.5mgkg（-1））后，CLP小鼠的死亡率明显降低，临床评分明显改善，腹腔注射顺铂后，CLP小鼠腹腔液中IL-6和TNF-α水平明显降低。顺铂虽无直接杀菌作用，但在CLP发病后24和72 h，腹腔和血液中的细菌数量明显减少。此外，在体内吞噬和杀伤实验表明，来自腹膜的巨噬细胞的能力显着增加与顺铂治疗（5，10，15 M）的革兰氏阳性菌（粪肠球菌）和革兰氏阴性菌（大肠杆菌）。这与从CD 11b（+）F4/80（高）CD 206（-）到CD 11b（+）F4/80（低）CD 206（-）M1组的巨噬细胞表型极化有关。这些发现强调了低剂量顺铂在脓毒症治疗中的重要性。
Sepsis is a systemic inflammatory response to infection, and early responses of macrophages are vital in controlling the infected microorganisms. We used a cecal ligation and puncture (CLP) model of sepsis to determine the role of cisplatin (0.1, 0.5 and 1mgkg(-1)) with respect to peritoneal macrophages, controlling peritoneal/blood bacterial infection, and systemic inflammation. We found that mice which received low-dose (0.1 and 0.5mgkg(-1)) i.p. cisplatin had lower mortality rate and improved clinical scores compared with mice in normal saline-treated group, and the level of IL-6 and TNF- was significantly reduced after cisplatin administration in peritoneal fluid of mice underwent CLP. Although cisplatin had no directly bactericidal ability, the numbers of bacteria in peritoneal and blood were significantly reduced at 24 and 72h after the onset of CLP. Besides, in vivo phagocytosis and killing assay showed that the ability of macrophage derived from peritoneum was significantly increased with cisplatin treatment (5, 10, and 15M) for both gram-positive (Enterococcus faecalis) and gram-negative (Escherichia coli) bacteria. This was associated with the macrophage phenotype polarization from CD11b(+)F4/80(high)CD206(-) to CD11b(+)F4/80(low)CD206(-) M1 group. These findings underscore the importance of low-dose cisplatin in the treatment of sepsis.