中性粒细胞胞外诱捕网通过激活NLRP3炎症小体诱导人肺微血管内皮细胞焦亡  

Neutrophil extracellular traps induce pyroptosis of human pulmonary microvascular endothelial cells by activating NLRP3 inflammasome

作　　者：赵佩佩 朱嘉睿 李飞飞 张岑 张思功[3] Zhao Peipei;Zhu Jiarui;Li Feifei;Zhang Cen;Zhang Sigong(The Second Clinical Medical School,Lanzhou University,Lanzhou 730030,China;Cuiying Biomedical Research Center,The Second Hospital of Lanzhou University,Lanzhou 730030,China;Department of Rheumatology,The Second Hospital of Lanzhou University,Lanzhou 730030,China)

机构地区：[1]兰州大学第二临床医学院,甘肃兰州730030 [2]兰州大学第二医院萃英生物医学研究中心,甘肃兰州730030 [3]兰州大学第二医院风湿免疫科,甘肃兰州730030

出　　处：《兰州大学学报（医学版）》2024年第5期6-13,共8页Journal of Lanzhou University（Medical Sciences）

基　　金：国家自然科学基金资助项目(82060302,82260325);甘肃省教育科技创新项目(2022B-051);兰州大学医学创新发展计划资助项目(lzuyxcx-2022-168);兰州大学第二医院萃英科技创新计划资助项目(CY2021-MS-A04,CY2021-QN-B02)。

摘　　要：目的探讨中性粒细胞胞外诱捕网作用于肺微血管内皮细胞并诱发内皮细胞死亡的具体机制。方法以200 ng/mL的体外分离的中性粒细胞胞外诱捕网刺激人肺微血管内皮细胞,碘化丙锭染色法检测细胞死亡情况,蛋白质印迹法和免疫荧光法检测焦亡标记物。结果与对照组相比,中性粒细胞胞外诱捕网刺激后的肺微血管内皮细胞死亡加剧,NLRP3炎症小体和焦亡相关标记物GSDMD、N-GSDMD表达明显升高,NLRP3抑制剂MCC950预处理可有效减弱NLRP3的激活,抑制细胞焦亡的发生。结论中性粒细胞胞外诱捕网可通过激活NLRP3炎症小体诱发人肺微血管内皮细胞焦亡。Objective To investigate into the specific mechanism of neutrophil extracellular traps acting on pulmonary microvascular endothelial cells and inducing endothelial cell death.Methods Human pulmonary microvascular endothelial cells were stimulated with NETs 200 ng/mL isolated in vitro.The cell death was detected by PI staining.The pyroptosis markers were detected by Western blot and immunofluorescence.Results Compared with the control group,the death of human pulmonary microvascular endothelial cells was increased after stimulation with neutrophil extracellular traps.The expression of NLRP3 inflammasome and pyroptosis related markers GSDMD,N-GSDMD were significantly increased.Pretreatment of NLRP3 inhibitor MCC950 effectively weakened the activation of NLRP3 and further inhibited the occurrence of pyroptosis.Conclusion Neutrophil extracellular traps promote the pyroptosis of human lung microvascular endothelial cells by activating the NLRP3 inflammasome.

关 键 词：中性粒细胞胞外诱捕网 肺微血管内皮细胞 NLRP3炎症小体 细胞焦亡 

分 类 号：R593.2[医药卫生—内科学]