中文摘要:
有機物不充分燃燒產生的炭黑超細顆粒(nCB)長期經呼吸道暴露可誘發白介素 - 17A 依賴性肺氣腫,但該類顆粒能否、以及如何改變機體針對肺癌的免疫應答尚不明確。本研究證實,nCB 顆粒暴露會提升程序性死亡配體 1?/ 程序性死亡配體 2?/CD206?抗原提呈細胞、耗竭型 T 細胞與調節性 T 細胞的占比。胞內蓄積 nCB 顆粒的肺巨噬細胞出現線粒體結構特異性損傷、有氧呼吸水平下降;巨噬細胞持續激活缺氧誘導因子 1α 通路,促使糖酵解增強、乳酸大量生成,最終在多種非小細胞肺癌小鼠模型中形成免疫抑制型腫瘤微環境。將經 nCB 暴露的野生型小鼠肺抗原提呈細胞過繼轉移至易感小鼠體內后,受試小鼠腫瘤發生率升高且腫瘤出現早期轉移。綜上,nCB 暴露通過重塑肺巨噬細胞代謝模式誘導免疫抑制,進而加速肺癌發生發展。
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.
論文信息:
論文題目:Chronic exposure to carbon black ultrafine particles reprograms macrophage metabolism and accelerates lung cancer
期刊名稱:Science Advances
時間期卷:Vol 8, Issue46(2022)
在線時間:2022年11月16日
DOI: 10.1126/sciadv.abq0615
產品信息:
貨號:CP-005-005
規格:5ml+5ml
品牌:Liposoma
產地:荷蘭
名稱:Clodronate Liposomes&Control Liposomes
辦事處:靶點科技
Clodronate Liposomes氯膦酸鹽脂質體鼻腔滴鼻清除肺泡巨噬細胞。荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Science Advances:長期暴露于超細炭黑顆??芍鼐幊叹奘杉毎x并加速肺癌進展。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體清除巨噬細胞的材料和方法:
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 月齡 Pts4d/d 小鼠在 1.5 周內分 5 次給予超細炭黑顆粒(nCB,單次給藥 0.5 毫克 / 50 微升)氣道暴露。在第 3 次 nCB 給藥結束后,連續 3 周經鼻腔滴注氯膦酸脂質體或對照空脂質體(品牌:Liposoma),每周給藥 3 次。末次脂質體處理 2 天后處死小鼠并開展各項檢測。
巨噬細胞清除材料和方法文獻截圖:長期暴露于超細炭黑顆??芍鼐幊叹奘杉毎x并加速肺癌進展
