中文摘要：

有機(jī)物不充分燃燒產(chǎn)生的炭黑超細(xì)顆粒（nCB）長期經(jīng)呼吸道暴露可誘發(fā)白介素 - 17A 依賴性肺氣腫，但該類顆粒能否、以及如何改變機(jī)體針對肺癌的免疫應(yīng)答尚不明確。本研究證實(shí)，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(xì)胞、耗竭型 T 細(xì)胞與調(diào)節(jié)性 T 細(xì)胞的占比。胞內(nèi)蓄積 nCB 顆粒的肺巨噬細(xì)胞出現(xiàn)線粒體結(jié)構(gòu)特異性損傷、有氧呼吸水平下降；巨噬細(xì)胞持續(xù)激活缺氧誘導(dǎo)因子 1α 通路，促使糖酵解增強(qiáng)、乳酸大量生成，最終在多種非小細(xì)胞肺癌小鼠模型中形成免疫抑制型腫瘤微環(huán)境。將經(jīng) nCB 暴露的野生型小鼠肺抗原提呈細(xì)胞過繼轉(zhuǎn)移至易感小鼠體內(nèi)后，受試小鼠腫瘤發(fā)生率升高且腫瘤出現(xiàn)早期轉(zhuǎn)移。綜上，nCB 暴露通過重塑肺巨噬細(xì)胞代謝模式誘導(dǎo)免疫抑制，進(jìn)而加速肺癌發(fā)生發(fā)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(shí)間期卷：Vol 8, Issue46(2022)

在線時(shí)間：2022年11月16日

DOI: 10.1126/sciadv.abq0615

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體鼻腔滴鼻清除肺泡巨噬細(xì)胞。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Science Advances：長期暴露于超細(xì)炭黑顆粒可重編程巨噬細(xì)胞代謝并加速肺癌進(jìn)展。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞的材料和方法：

Macrophage depletion

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(nèi)分 5 次給予超細(xì)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(jié)束后，連續(xù) 3 周經(jīng)鼻腔滴注氯膦酸脂質(zhì)體或?qū)φ湛罩|(zhì)體（品牌：Liposoma），每周給藥 3 次。末次脂質(zhì)體處理 2 天后處死小鼠并開展各項(xiàng)檢測。

巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖：長期暴露于超細(xì)炭黑顆粒可重編程巨噬細(xì)胞代謝并加速肺癌進(jìn)展