IL-10+IL-4能提高M2巨噬细胞表型和嗜酸性粒细胞的迁移  

IL-10 and IL-4 enhance phenotype of M2 macrophages and eosinophil migration

作　　者：童晓鹏[1] 杨波[1] 门连超 张群辉[1] 

机构地区：[1]西藏民族大学,咸阳712082

出　　处：《中国免疫学杂志》2016年第9期1309-1314,1318,共7页Chinese Journal of Immunology

基　　金：国家自然科学基金(81560732);西藏自治区自然科学基金项目(2015ZR-13-18)

摘　　要：目的:研究论证IL-10是否能通过诱导IL-4来提高M2。方法:用C57BL/6J鼠中的骨髓细胞诱导M-CSF诱导的骨髓源巨噬细胞,利用小鼠全基因组版本进行转录,进而嗜酸性粒细胞的迁移实验,体内巨噬细胞的转移实验。结果:研究发现在M-CSF诱导的BMDMs中通过IL-4、IL-10及IL-4+IL-10诱导来分析M2巨噬细胞,IL-10通过IL-4来提高M2a标志物的表达,此外,IL-4和IL-10诱导产生CCL24时起协同作用。在GM-CSF诱导的BMDMs中CCL24的表达提高。CCL24是CCR3的激动剂和嗜酸性粒细胞的趋化因子。在体外,IL-4+IL-10激活的巨噬细胞产生大量的CCL24,并且能提高嗜酸性粒细胞的迁移。这个过程能被抗CCL24抗体抑制。IL-4+IL-10激活的巨噬细胞转移到C57BL/6J小鼠的腹膜,这能增加嗜酸性粒细胞浸润腹膜腔。结论:IL-4+IL-10激活的巨噬细胞能增强M2a巨噬细胞相关基因的表达,提高CCL24的产生和嗜酸性粒细胞的浸润,导致嗜酸性粒细胞相关疾病的发生。Objective：To clarify whether IL-10 enhanced the M2 phenotype induced by IL-4.Methods：M-CSF induced bone marrow-derived macrophages（BMDMs） were generated from C57 BL/6J mice bone marrow cells.The RNA transcriptional profile was evaluated using the Mouse Whole Genome.We performed in vitro eosinophil migration assay and in vivo macrophage transfer.Results：The results showed that IL-10 enhanced gene expression of M2 a markers induced by IL-4 in M-CSF-induced BMDMs.Moreover,IL-4and IL-10 synergistically induced CCL24（Eotaxin-2） production.Enhanced CCL24 expression was also observed in GM-CSF-induced BMDMs and zymosan-elicited,thioglycolate-elicited and naive peritoneal macrophages.CCL24 was a CCR3 agonist and an eosinophil chemoattractant.In vitro,IL-4 ＋ IL-10-stimulated macrophages produced a large amount of CCL24 and increased eosinophil migration,which was inhibited by anti-CCL24 antibody.IL-4 ＋ IL-10-stimulated（but not IL-4 or IL-10 alone） macrophages transferred into the peritoneumof C57 BL/6J mice increased eosinophil infiltration into the peritoneal cavity.Conclusion：These results demonstrate that IL-4 ＋ IL-10-simulated macrophages have enhanced M2 a macrophage-related gene expression,CCL24 production and eosinophil infiltration-inducing activity,thereby suggesting theircontribution to eosinophil-related diseases.

关 键 词：IL-4 IL-10 CCL24 嗜酸性粒细胞 M2a巨噬细胞 

分 类 号：R392.12[医药卫生—免疫学]