A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice
A single intratracheal instillation of single-walled carbon nanotubes induced early lung fibrosis and subchronic tissue damage in mice
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DOI：
10.1007/s00204-011-0655-8
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发表时间：
2011-09-01
影响因子：
6.1
通讯作者：
Choi, Kyunghee
中科院分区：
文献类型：
--
作者：
Park, Eun-Jung;Roh, Jinkyu;Choi, Kyunghee
大量的纳米材料可能到达自然和职业环境。这代表着潜在的健康危害。人们预测碳纳米管可能导致间皮瘤等毒性和石棉等纤维化。为了确定SWCNTs诱导的显性免疫应答，我们研究了单壁碳纳米管（SWCNT）单次给药后一段时间内细支气管肺泡灌洗（BAL）细胞的组成、细胞因子和胶原的分泌、组织病理学、蛋白质表达和细胞表型。在我们的研究结果中，总细胞和巨噬细胞的数量一直保持在上调水平，直到第28天，中性粒细胞在第1天迅速增加，淋巴细胞从第7天开始增加。在BAL液中，促炎细胞因子在第1天迅速增加，并在整个实验期间保持上调水平。IL-12和IL-10在给药后第1天迅速升高，并保持在相似水平直到第28天。ifn - γ和IL-4在第1天达到最大值，IL-5、tgf - β和胶原蛋白在第7天达到最大值。IL-13和IL-17呈时间依赖性增加。第7、14天B细胞和细胞毒性T细胞分布明显增加，第7、14天组织病理学观察到纤维化病变。caspase-3、p53、COL1A1、COX-2、iNOS、MMP-9、MMP-2的表达也在第7天和第14天显著升高。此外，间皮素、iNOS、MMP-9和p53的表达上调至第28天。基于这些发现，我们认为单次气管内灌注SWCNTs可诱导早期肺纤维化和亚慢性组织损伤。
Large amounts of nanomaterials may reach both the natural and occupational environments. This represents a potential health hazard. People have forecasted that CNTs may lead to the toxicity such as mesothelioma and fibrosis like asbestos. To identify dominant immune responses induced by SWCNTs, we investigated the composition of bronchioalveolar lavage (BAL) cells, the secretion of cytokine and collagen, histopathology, protein expression, and cell phenotypes over time after a single administration of single-walled carbon nanotubes (SWCNT). In our results, the number of total cells and macrophages remained at the up-regulated level until Day 28, neutrophils rapidly increased at Day 1, and lymphocytes increased from Day 7. In the BAL fluid, pro-inflammatory cytokines rapidly increased at Day 1 and remained at an up-regulated level throughout the experimental period. IL-12 and IL-10 rapidly increased at Day 1 after administration and remained at a similar level until Day 28. IFN-gamma and IL-4 reached the maximum at Day 1, and IL-5, TGF-beta, and collagen reached the maximum at Day 7. IL-13 and IL-17 increased in a time-dependent manner. The distribution of B cells and cytotoxic T cells markedly increased at Days 7 and 14, and fibrotic lesions were histopathologically observed at Days 7 and 14. The expressions of caspase-3, p53, COL1A1, COX-2, iNOS, MMP-9, and MMP-2 were also markedly increased at Days 7 and 14. In addition, the expression of mesothelin, iNOS, MMP-9, and p53 was up-regulated until Day 28. Based on these findings, we suggest that a single intratracheal instillation of SWCNTs may induce early lung fibrosis and subchronic tissue damage.