Wen Haitao, Hogaboam Cory M, Lukacs Nicholas W, Cook Donald N, Lira Sergio A, Kunkel Steven L
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
Eur J Immunol. 2007 Sep;37(9):2487-98. doi: 10.1002/eji.200737370.
In our initial studies we found that naïve CCR6-deficient (CCR6(-/-)) C57BL/6 mice possessed significantly lower number of both F4/80(+) macrophages and dendritic cells (DC), but higher number of B cells in the peritoneal cavity, as compared to naïve wild type (WT) controls. Furthermore, peritoneal macrophages isolated from CCR6(-/-) mice expressed significantly lower levels of inflammatory cytokines and nitric oxide following lipopolysaccharide (LPS)stimulation, as compared to WT macrophages. In a severe experimental peritonitis model induced by cecal ligation and puncture (CLP), CCR6(-/-) mice were protected when compared with WT controls. At 24 h following the induction of peritonitis, CCR6(-/-) mice exhibited significantly lower levels of inflammatory cytokines/chemokines in both the peritoneal cavity and blood. Interestingly, DC recruitment into the peritoneal cavity was impaired in CCR6(-/-) mice during the evolution of CLP-induced peritonitis. Peritoneal macrophages isolated from surviving CCR6(-/-) mice 3 days after CLP-induced peritonitis exhibited an enhanced LPS response compared with similarly treated WT peritoneal macrophages. These data illustrate that CCR6 deficiency alters the innate response via attenuating the hyperactive local and systemic inflammatory response during CLP-induced peritonitis.
在我们最初的研究中，我们发现，与单纯的野生型（WT）对照小鼠相比，未经致敏的CCR6缺陷型（CCR6(-/-)）C57BL/6小鼠腹腔内F4/80(+)巨噬细胞和树突状细胞（DC）的数量显著减少，但B细胞数量更多。此外，与野生型巨噬细胞相比，从CCR6(-/-)小鼠分离的腹腔巨噬细胞在脂多糖（LPS）刺激后炎症细胞因子和一氧化氮的表达水平显著降低。在盲肠结扎和穿刺（CLP）诱导的严重实验性腹膜炎模型中，与野生型对照相比，CCR6(-/-)小鼠受到了保护。腹膜炎诱导后24小时，CCR6(-/-)小鼠腹腔和血液中的炎症细胞因子/趋化因子水平显著降低。有趣的是，在CLP诱导的腹膜炎发展过程中，CCR6(-/-)小鼠腹腔内DC的募集受损。与同样处理的野生型腹腔巨噬细胞相比，CLP诱导的腹膜炎3天后从存活的CCR6(-/-)小鼠分离的腹腔巨噬细胞对LPS的反应增强。这些数据表明，CCR6缺陷通过减弱CLP诱导的腹膜炎期间过度活跃的局部和全身炎症反应来改变先天免疫反应。
