中性粒细胞胞外诱捕网通过诱导巨噬细胞M2型极化促进非小细胞肺癌增殖和侵袭  

Neutrophil extracellular traps promote proliferation and invasion of NSCLC by inducing M2-type polarization of macrophages

作　　者：苏莹[1] 马丽丽[1] 柳江[1] 韩忠诚[1] SU Ying;MA Lili;LIU Jiang;HAN Zhongcheng(Department of Oncology,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi 830000,China)

机构地区：[1]新疆维吾尔自治区人民医院肿瘤科,乌鲁木齐830000

出　　处：《中国免疫学杂志》2023年第3期472-477,共6页Chinese Journal of Immunology

基　　金：新疆维吾尔自治区自然科学基金项目(2019D01C100)。

摘　　要：目的:探究中性粒细胞胞外诱捕网(NETs)诱导巨噬细胞极化在非小细胞肺癌(NSCLC)增殖和侵袭中的作用及其相关机制。方法:采集28例NSCLC患者肿瘤组织及其癌旁组织,通过免疫组化检测PAD4和Arg-1表达水平。采用PMA/LPS和PMA/IL-4极化THP-1细胞为M1和M2型巨噬细胞的过程中加入NETs共孵育,qRT-PCR检测巨噬细胞iNOS、IL-6、TNF-α、Arg-1、IL-10和TGF-β表达水平。将各组M2型巨噬细胞与A549细胞共孵育,CCK8检测A549细胞增殖变化,Transwell检测细胞侵袭能力变化,qRT-PCR和Western blot检测细胞VEGF表达水平变化。结果:与癌旁组织比较,NSCLC患者肿瘤组织PAD4和Arg-1表达水平升高。在向M1型巨噬细胞极化过程中,加入NETs后巨噬细胞iNOS、IL-6、TNF-α表达水平降低,Arg-1、IL-10、TGF-β表达水平升高。在向M2型巨噬细胞极化过程中,加入NETs后巨噬细胞Arg-1、IL-10、TGF-β表达水平升高。与Control组比较,M2组A549细胞增殖、侵袭能力和VEGF表达水平升高。与M2组比较,M2+NETs组A549细胞增殖、侵袭能力和VEGF表达水平升高。结论:NETs通过诱导巨噬细胞向M2型极化,促进NSCLC增殖和侵袭。Objective:To investigate the role of neutrophil extracellular trap(NETs)induced macrophage polarization in proliferation and invasion of non-small cell lung cancer(NSCLC)and its related mechanisms.Methods:Tumor tissues and adjacent tissues of 28 NSCLC patients were collected and the expression levels of PAD4 and ARG-1 were detected by immunohistochemistry.The expression levels of iNOS,IL-6,TNF-α,ARG-1,IL-10 and TGF-βin macrophages were detected by qRT-PCR when PMA/LPS and PMA/IL-4-polarized THP-1 cells were incubated with NETs.M2 macrophages in each group were co-incubated with A549 cells.Proliferation of A549 cells were detected by CCK8,invasion ability of A549 cells were detected by Transwell,and expression level of VEGF was detected by qRT-PCR and Western blot.Results:Compared with adjacent tissues,the expression levels of PAD4 and ARG-1 in tumor tissues of NSCLC patients were increased.During the polarization to M1-type macrophages,the expression levels of iNOS,IL-6 and TNF-αin macrophages were decreased after co-incubation with NETs,while the expression levels of ARG-1,IL-10 and TGF-βwere increased.During the polarization of M2-type macrophages,the expression levels of ARG-1,IL-10 and TGF-βin macrophages increased after co-incubation with NETs.Compared with Control group,the proliferation,invasion and VEGF expression levels of A549 cells in M2 group were increased.Compared with M2 group,proliferation,invasion and VEGF expression levels of A549 cells in M2+NETs group were increased.Conclusion:NETs promote proliferation and invasion of NSCLC by inducing macrophage polarization to M2 type.

关 键 词：非小细胞肺癌 中性粒细胞胞外诱捕网 巨噬细胞 M2型极化 

分 类 号：R734.2[医药卫生—肿瘤]