Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes
Persistent Pleural Lesions and Inflammation by Pulmonary Exposure of Multiwalled Carbon Nanotubes
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多壁碳纳米管肺部暴露引起的持续性胸膜病变和炎症
DOI：
10.1021/acs.chemrestox.8b00067
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发表时间：
2018
影响因子：
4.1
通讯作者：
Tsuda Hiroyuki
中科院分区：
文献类型：
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作者：
Liao Dongping;Wang Qiqi;He Jiali;Alexander David B.;Abdelgied Mohamed;El-Gazzar Ahmed M.;Futakuchi Mitsuru;Suzui Masumi;Kanno Jun;Hirose Akihiko;Xu Jiegou;Tsuda Hiroyuki
在通过不同肺暴露方法给予多壁碳纳米管（MWCNTs）的啮齿动物中，发现了多壁碳纳米管（MWCNTs）从肺向胸膜腔的易位、纤维在胸膜组织中的沉积、胸膜纤维化的诱导和间皮细胞增殖。然而，移位和沉积以及随后的胸膜炎症是否与胸膜病变有关尚不清楚。本研究中，雄性F344大鼠以青绿石为阳性对照，以250 μg的剂量给予两种MWCNTs，每周2次/次，连续4周。末次给药后24 h和3个月处死大鼠进行肺、胸壁组织学检查；牺牲时收集胸腔灌洗液，观察胸膜炎症反应。结果表明，气管内喷射的MWCNTs与青绿石纤维一样，易位进入胸膜腔，沉积在胸膜内，诱导免疫细胞持续浸润胸膜腔，持续胸膜纤维化和间皮细胞增殖。胸腔灌洗液中检测到的MWCNT纤维数量与浸润免疫细胞数量相当，浸润免疫细胞以巨噬细胞为主。悬浮阵列法分析胸腔灌洗液中细胞因子结果显示，在末次喷药后24 h和3个月，IL-2、IL-18和IP-10水平均显著升高。体外增殖实验显示，IL-2、IL-18和IP-10的混合物，而不是单独使用这些细胞因子中的任何一种，都能促进人成纤维细胞和间皮细胞的增殖。这些结果表明，易位和沉积的MWCNTs诱导随后的胸膜炎症，并且IL-2、IL-18和IP-10的增加协同促进胸膜纤维化和间皮细胞增殖的发展。
Translocation of multiwalled carbon nanotubes (MWCNTs) from the lung to the pleural cavity, deposition of the fibers in the pleural tissue, induction of pleural fibrosis, and mesothelial proliferation have been found in rodents administered MWCNTs by different pulmonary exposure methods. However, whether the translocation and deposition and the subsequent pleural inflammation are associated with the pleural lesions is unclear. In the present study, male F344 rats were given 250 μg of two types of MWCNTs, with crocidolite as a positive control, 2 times/week for 4 weeks by intratracheal spraying. At 24 h and at 3 months after the last spraying, the rats were sacrificed for histological examination of the lung and chest wall; pleural cavity lavage was also collected at sacrifice for observation of pleural inflammatory reactions. The results indicated that intratracheally sprayed MWCNTs, like crocidolite fibers, translocated into the pleural cavity, deposited in the pleura, and induced persistent infiltration of immune cells into the pleural cavity, persistent pleural fibrosis, and mesothelial proliferation. The number of MWCNT fibers detected in the pleural cavity lavage was parallel to the number of infiltrating immune cells, which were mainly composed of macrophages. Analysis of cytokines in the fluids of the pleural cavity lavages by suspension array indicated that levels of IL-2, IL-18, and IP-10 were significantly increased both at 24 h and at 3 months after the last spraying. In vitro proliferation assays revealed that a mixture of IL-2, IL-18, and IP-10, but not any of these cytokines alone, promoted cell proliferation of human fibroblasts and mesothelial cells. These results suggest that translocated and deposited MWCNTs induce subsequent pleural inflammation and that increased IL-2, IL-18, and IP-10 synergistically promote the development of pleural fibrosis and mesothelial proliferation.