a Department of Biological Sciences, North Carolina State University , Raleigh , NC , USA.
b National Institute of Environmental Health Sciences , Durham , NC , USA.
Inhal Toxicol. 2019 Apr;31(5):192-202. doi: 10.1080/08958378.2019.1643955. Epub 2019 Jul 26.
Increasing evidence from rodent studies indicates that inhaled multi-walled carbon nanotubes (MWCNTs) have harmful effects on the lungs. In this study, we examined the effects of inhalation exposure to MWCNTs on allergen-induced airway inflammation and fibrosis. We hypothesized that inhalation pre-exposure to MWCNTs would render mice susceptible to developing allergic lung disease induced by house dust mite (HDM) allergen. Male B6C3F1/N mice were exposed by whole-body inhalation for 6 h a day, 5 d a week, for 30 d to air control or 0.06, 0.2, and 0.6 mg/m of MWCNTs. The exposure atmospheres were agglomerates (1.4-1.8 µm) composed of MWCNTs (average diameter 16 nm; average length 2.4 µm; 0.52% Ni). Mice then received 25 µg of HDM extract by intranasal instillation 6 times over 3 weeks. Necropsy was performed at 3 and 30 d after the final HDM dose to collect serum, bronchoalveolar lavage fluid (BALF), and lung tissue for histopathology. MWCNT exposure at the highest dose inhibited HDM-induced serum IgE levels, IL-13 protein levels in BALF, and airway mucus production. However, perivascular and peribronchiolar inflammatory lesions were observed in the lungs of mice at 3 d with MWCNT and HDM, but not MWCNT or HDM alone. Moreover, combined HDM and MWCNT exposure increased airway fibrosis in the lungs of mice. Inhalation pre-exposure to MWCNTs inhibited HDM-induced TH2 immune responses, yet this combined exposure resulted in vascular inflammation and airway fibrosis, indicating that MWCNT pre-exposure alters the immune response to allergens.
越来越多的啮齿动物研究证据表明,吸入多壁碳纳米管(MWCNTs)会对肺部造成有害影响。在这项研究中,我们研究了吸入 MWCNTs 暴露对变应原诱导的气道炎症和纤维化的影响。我们假设,MWCNTs 吸入预暴露会使小鼠易患由屋尘螨(HDM)变应原引起的过敏性肺部疾病。雄性 B6C3F1/N 小鼠通过全身吸入暴露,每天 6 小时,每周 5 天,连续 30 天,分别暴露于空气对照或 0.06、0.2 和 0.6mg/m 的 MWCNTs 中。暴露的大气是由 MWCNTs(平均直径 16nm;平均长度 2.4μm;0.52%Ni)组成的团聚体(1.4-1.8μm)。然后,小鼠通过鼻腔内滴注接受 25μg 的 HDM 提取物 6 次,共 3 周。在最后一次 HDM 剂量后 3 和 30 天进行尸检,以收集血清、支气管肺泡灌洗液(BALF)和肺组织进行组织病理学检查。在最高剂量的 MWCNT 暴露下,HDM 诱导的血清 IgE 水平、BALF 中的 IL-13 蛋白水平和气道粘液产生受到抑制。然而,在暴露于 MWCNT 和 HDM 的小鼠肺部中,在第 3 天观察到血管周围和细支气管周围的炎症病变,但在单独暴露于 MWCNT 或 HDM 时则没有。此外,联合暴露于 HDM 和 MWCNT 增加了小鼠肺部的气道纤维化。MWCNTs 吸入预暴露抑制了 HDM 诱导的 TH2 免疫反应,但这种联合暴露导致血管炎症和气道纤维化,表明 MWCNT 预暴露改变了对过敏原的免疫反应。