Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells
Mesothelioma response to carbon nanotubes is associated with an early and selective accumulation of immunosuppressive monocytic cells
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DOI：
10.1186/s12989-016-0158-0
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发表时间：
2016-08-23
影响因子：
10
通讯作者：
Lison, Dominique
中科院分区：
文献类型：
--
作者：
Huaux, Francois;de Bousies, Virginie d'Ursel;Lison, Dominique
背景：一些工程碳纳米管（CNT）具有类似石棉的毒性，特别是它们诱发间皮瘤的能力，是引起公众健康担忧的一个严重原因。在这里，我们发现致癌性 CNT 会诱导早期持续的免疫抑制反应，其特征是单核细胞骨髓源性抑制细胞 (M-MDSC) 的积累，从而抵消肿瘤细胞的有效免疫监视。方法：向 Wistar 大鼠和 C57BL/6 小鼠腹腔注射致癌性多壁 Mitsui-7 CNT (CNT-7) 或青石棉。评估腹膜间皮瘤的发展和免疫细胞积累直至 12 个月。通过流式细胞术记录 CD11b/c 和 His48 的表达来鉴定白细胞亚群。通过与活化的脾细胞共培养测定来评估纯化的腹膜白细胞对 T 淋巴细胞的免疫抑制活性。 结果：我们证明，将长和短的间皮瘤性 CNT-7 注射到大鼠腹膜腔中，会像石棉一样诱导单核细胞（CD11b/c（int）和 His48（hi））的早期选择性积累，这些细胞具有抑制 T 淋巴细胞多克隆活化的能力，并对应于M-MDSC。在 CNT-7 治疗的大鼠中，腹膜 M-MDSC 在腹膜间皮瘤的发展过程中持续存在，但在注射非致癌性 CNT（CNT-M、CNT-T）后仅短暂恢复。腹膜 M-MDSC 在对间皮瘤发展具有抵抗力的小鼠中不会积聚。结论：我们的数据为 CNT 诱导的初始致病事件提供了新的见解，为导致间皮瘤发展的不良结果途径添加了新的组成部分。致癌性 CNT 暴露后 M-MDSC 响应的特异性突出了该响应对于检测新纳米材料致癌能力的兴趣。
Background: The asbestos-like toxicity of some engineered carbon nanotubes (CNT), notably their capacity to induce mesothelioma, is a serious cause of concern for public health. Here we show that carcinogenic CNT induce an early and sustained immunosuppressive response characterized by the accumulation of monocytic Myeloid Derived Suppressor Cells (M-MDSC) that counteract effective immune surveillance of tumor cells.Methods: Wistar rats and C57BL/6 mice were intraperitoneally injected with carcinogenic multi-walled Mitsui-7 CNT (CNT-7) or crocidolite asbestos. Peritoneal mesothelioma development and immune cell accumulation were assessed until 12 months. Leukocyte sub-populations were identified by recording expression of CD11b/c and His48 by flow cytometry. The immunosuppressive activity on T lymphocytes of purified peritoneal leukocytes was assessed in a co-culture assay with activated spleen cells.Results: We demonstrate that long and short mesotheliomagenic CNT-7 injected in the peritoneal cavity of rats induced, like asbestos, an early and selective accumulation of monocytic cells (CD11b/c(int) and His48(hi)) which possess the ability to suppress polyclonal activation of T lymphocytes and correspond to M-MDSC. Peritoneal M-MDSC persisted during the development of peritoneal mesothelioma in CNT-7-treated rats but were only transiently recruited after non-carcinogenic CNT (CNT-M, CNT-T) injection. Peritoneal M-MDSC did not accumulate in mice which are resistant to mesothelioma development.Conclusions: Our data provide new insights into the initial pathogenic events induced by CNT, adding a new component to the adverse outcome pathway leading to mesothelioma development. The specificity of the M-MDSC response after carcinogenic CNT exposure highlights the interest of this response for detecting the ability of new nanomaterials to cause cancer.