中文摘要:
有机物不充分燃烧产生的炭黑超细颗粒(nCB)长期经呼吸道暴露可诱发白介素 - 17A 依赖性肺气肿,但该类颗粒能否、以及如何改变机体针对肺癌的免疫应答尚不明确。本研究证实,nCB 颗粒暴露会提升程序性死亡配体 1⁺/ 程序性死亡配体 2⁺/CD206⁺抗原提呈细胞、耗竭型 T 细胞与调节性 T 细胞的占比。胞内蓄积 nCB 颗粒的肺巨噬细胞出现线粒体结构特异性损伤、有氧呼吸水平下降;巨噬细胞持续激活缺氧诱导因子 1α 通路,促使糖酵解增强、乳酸大量生成,最终在多种非小细胞肺癌小鼠模型中形成免疫抑制型肿瘤微环境。将经 nCB 暴露的野生型小鼠肺抗原提呈细胞过继转移至易感小鼠体内后,受试小鼠肿瘤发生率升高且肿瘤出现早期转移。综上,nCB 暴露通过重塑肺巨噬细胞代谢模式诱导免疫抑制,进而加速肺癌发生发展。
英文摘要:
Chronic exposure to airborne carbon black ultrafine (nCB) particles generated from incomplete combustion of organic matter drives IL-17A–dependent emphysema. However, whether and how they alter the immune responses to lung cancer remains unknown. Here, we show that exposure to nCB particles increased PD-L1+ PD-L2+ CD206+ antigen-presenting cells (APCs), exhausted T cells, and Treg cells. Lung macrophages that harbored nCB particles showed selective mitochondrial structure damage and decreased oxidative respiration. Lung macrophages sustained the HIF1α axis that increased glycolysis and lactate production, culminating in an immunosuppressive microenvironment in multiple mouse models of non–small cell lung cancers. Adoptive transfer of lung APCs from nCB-exposed wild type to susceptible mice increased tumor incidence and caused early metastasis. Our findings show that nCB exposure metabolically rewires lung macrophages to promote immunosuppression and accelerates the development of lung cancer.
论文信息:
论文题目:Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer
期刊名称:Science Advances
时间期卷:Vol 8, Issue46(2022)
在线时间:2022年11月16日
DOI: 10.1126/sciadv.abq0615
产品信息:
货号:CP-005-005
规格:5ml+5ml
品牌:Liposoma
产地:荷兰
名称:Clodronate Liposomes&Control Liposomes
办事处:靶点科技
Clodronate Liposomes氯膦酸盐脂质体鼻腔滴鼻清除肺泡巨噬细胞。荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Science Advances:长期暴露于超细炭黑颗粒可重编程巨噬细胞代谢并加速肺癌进展。

Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除巨噬细胞的材料和方法:
Pts4d/d mice age at 3 months were exposed to five doses of nCB (0.5 mg/50 μl) in 1.5 weeks. Mice were given 50 μl of clodronate liposome or control liposome (Liposoma) intranasally for 3 weeks (three times/week) after the third dose of nCB. Mice were euthanized for analysis 2 days after the final clodronate treatment.
3 月龄 Pts4d/d 小鼠在 1.5 周内分 5 次给予超细炭黑颗粒(nCB,单次给药 0.5 毫克 / 50 微升)气道暴露。在第 3 次 nCB 给药结束后,连续 3 周经鼻腔滴注氯膦酸脂质体或对照空脂质体(品牌:Liposoma),每周给药 3 次。末次脂质体处理 2 天后处死小鼠并开展各项检测。
巨噬细胞清除材料和方法文献截图:长期暴露于超细炭黑颗粒可重编程巨噬细胞代谢并加速肺癌进展
