Multi-walled carbon nanotubes activate and shift polarization of pulmonary macrophages and dendritic cells in an in vivo model of chronic obstructive lung disease
Multi-walled carbon nanotubes activate and shift polarization of pulmonary macrophages and dendritic cells in an in vivo model of chronic obstructive lung disease
复制标题
DOI：
10.1080/17435390.2019.1663954
复制
发表时间：
2019-09-23
期刊：
影响因子：
5
通讯作者：
Blank, Fabian
中科院分区：
文献类型：
--
作者：
Beyeler, Seraina;Steiner, Selina;Blank, Fabian
随着纳米技术的长足进步，人们越来越关注与吸入纳米材料（如多壁碳纳米管）有关的可能的不良健康影响。特别是，患有慢性呼吸系统疾病（如慢性阻塞性肺病（COPD））的个体可能更容易受到与吸入MWCNT相关的不良健康影响。因此，需要及时澄清此类吸入纳米材料的危害评估。在本研究中，通过将动物暴露于0.08 μ g/cm（2）的多壁碳纳米管（通过气管内滴注给药），使用COPD小鼠模型评估了这一点。多壁碳纳米管治疗诱导COPD小鼠支气管肺泡灌洗液（BALF）中肺泡巨噬细胞（AM phi）的积累，从24 h增加到7 d。在COPD小鼠中，MWCNT诱导巨噬细胞极化的动态变化，如通过CD 38和CD 206的表达所测量的，并且增加AM phi和肺实质巨噬细胞（LPM phi）活化，同时上调共刺激标志物CD 40和CD 80。此外，多壁碳纳米管处理增加了肺树突状细胞（DC）的频率，导致CD 11b（+）CD 103（-）DC亚群的扩增。虽然多壁碳纳米管没有触发肺功能或结构的变化，他们诱导了COPD小鼠muc 5AC转录表达增加。我们的数据提供了初步证据，吸入多壁碳纳米管影响肺粘膜免疫系统，通过改变抗原呈递细胞群的数量，表型和活化状态。将这些小鼠体内发现外推至人肺MWCNT暴露，在处理可吸入纳米纤维时限制暴露需要谨慎。
With substantial progress of nanotechnology, there is rising concern about possible adverse health effects related to inhalation of nanomaterials, such as multi-walled carbon nanotubes (MWCNT). In particular, individuals with chronic respiratory disorders, such as chronic obstructive pulmonary disease (COPD), may potentially be more susceptible to adverse health effects related to inhaled MWCNT. Hazard assessment of such inhaled nanomaterials therefore requires timely clarification. This was assessed in this study using a mouse model of COPD by exposing animals to 0.08 mu g/cm(2) of MWCNT administered by intratracheal instillation. Treatment with MWCNT induced an accumulation of alveolar macrophages (AM phi) in bronchoalveolar lavage fluid (BALF) in COPD mice that increased from 24 h to 7 d. In COPD mice, MWCNT induced a dynamic shift in macrophage polarization as measured by expression of CD38 and CD206, and increased AM phi and lung parenchyma macrophage (LPM phi) activation with upregulation of co-stimulatory markers CD40 and CD80. Moreover, MWCNT treatment increased the frequencies of pulmonary dendritic cells (DC), leading to an expansion of the CD11b(+)CD103(-) DC subset. Although MWCNT did not trigger lung functional or structural changes, they induced an increased expression of the muc5AC transcript in mice with COPD. Our data provide initial evidence that inhaled MWCNT affect the pulmonary mucosal immune system by altering the numbers, phenotype, and activation status of antigen-presenting cell populations. Extrapolating these in vivo mouse findings to human pulmonary MWCNT exposure, caution is warranted in limiting exposure when handling inhalable nanofibers.