脂多糖对蜕膜NK细胞表达NKG2D水平的促进作用

为探讨脂多糖(LPS)及其受体TLR4相互作用并影响蜕膜NK细胞的可能机制,在孕E6.5给BALB/c×C57BL/6孕鼠腹腔注射LPS,而E10.5采用流式细胞术检测小鼠蜕膜NKG2D+TGF-β-NK细胞构成比,计算小鼠胚胎吸收率。此外,采用磁珠亲和细胞分选术纯化E10.5小鼠蜕膜NK细胞并培养,用LPS刺激所培养的细胞,并观察刺激后NK细胞表达NKG2D水平的变化。研究发现,在体内和体外实验中LPS刺激均可显著增高BALB/c×C57BL/6孕鼠蜕膜NK细胞NKG2D的表达水平,其中腹腔注射可显著增高胚胎吸收率。在体外细胞培养实验中,预先在培养基中加入抗TLR4抗体,则LPS刺激后细胞NKG2D表达水平无显著升高。这些结果提示,LPS与TLR4相互作用可增强小鼠蜕膜NK细胞NKG2D的表达,而NKG2D的过高表达不利于同种异基因妊娠成功。

Up-regulation of NKG2D expression in decidual NK cells induced by LPS

To investigate the possible mechanisms by which LPS and its specific receptor TLR4 interact and modulate function of decidual NK cells,LPS was injected intraperitoneally into pregnant BALB×C57BL/6 mice on embryonic day E6.5,the proportion of decidual NKG2D+TGF-β-NK cells was determined by flow cytometry and the percentage of embryo resorption was investigated on E10.5.In addition,decidual NK cells were purified by magnetic affinity cell sorting on E10.5 and incubated in the presence of LPS.The expression pattern of NKG2D by NK cells in response to LPS stimulation was determined.It showed that NKG2D expression was increased by LPS in both in vivo and in vitro experiments,and that the percentage of embryo resorption was increased after intraperitoneal LPS injection.In the in vitro cell culture system,no up-regulation of NKG2D expression was observed if the cells were pre-incubated with anti-TLR4 antibody before LPS stimulation.These results suggest that LPS interacts with TLR4,up-regulates NKG2D expression in decidual NK cells,and over-expressed NKG2D may be harmful to allogeneic pregnancy.