Group II innate lymphoid cells and microvascular dysfunction from pulmonary titanium dioxide nanoparticle exposure

被引:19
作者
Abukabda, Alaeddin Bashir [1 ,2 ]
McBride, Carroll Rolland [1 ,2 ]
Batchelor, Thomas Paul [1 ,2 ]
Goldsmith, William Travis [1 ,2 ]
Bowdridge, Elizabeth Compton [1 ,2 ]
Garner, Krista Lee [1 ,2 ]
Friend, Sherri [3 ]
Nurkiewicz, Timothy Robert [1 ,2 ,3 ]
机构
[1] West Virginia Univ, Robert C Byrd Hlth Sci Ctr, Sch Med, Dept Physiol & Pharmacol, 64 Med Ctr Dr, Morgantown, WV 26505 USA
[2] West Virginia Univ, Sch Med, Toxicol Working Grp, Morgantown, WV 26505 USA
[3] NIOSH, Morgantown, WV USA
来源
PARTICLE AND FIBRE TOXICOLOGY | 2018年 / 15卷
关键词
Engineered nanomaterials; Titanium dioxide nanoparticles; Microcirculation; Innate lymphoid cells; Inflammation; DEPENDENT MODULATION; AIRWAY INFLAMMATION; RECEPTOR ST2; MURINE MODEL; IL-33; INHALATION; ALVEOLAR; IMMUNITY; DISRUPTS; PROMOTES;
D O I
10.1186/s12989-018-0280-2
中图分类号
R99 [毒物学(毒理学)];
学科分类号
100405 ;
摘要
Background: The cardiovascular effects of pulmonary exposure to engineered nanomaterials (ENM) are poorly understood, and the reproductive consequences are even less understood. Inflammation remains the most frequently explored mechanism of ENM toxicity. However, the key mediators and steps between lung exposure and uterine health remain to be fully defined. The purpose of this study was to determine the uterine inflammatory and vascular effects of pulmonary exposure to titanium dioxide nanoparticles (nano-TiO2). We hypothesized that pulmonary nano-TiO2 exposure initiates a Th2 inflammatory response mediated by Group II innate lymphoid cells (ILC2), which may be associated with an impairment in uterine microvascular reactivity. Methods: Female, virgin, Sprague-Dawley rats (8-12weeks) were exposed to 100g of nano-TiO2 via intratracheal instillation 24h prior to microvascular assessments. Serial blood samples were obtained at 0, 1, 2 and 4h post-exposure for multiplex cytokine analysis. ILC2 numbers in the lungs were determined. ILC2s were isolated and phosphorylated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappa B) levels were measured. Pressure myography was used to assess vascular reactivity of isolated radial arterioles. Results: Pulmonary nano-TiO2 exposure was associated with an increase in IL-1 ss, 4, 5 and 13 and TNF- alpha 4 h post-exposure, indicative of an innate Th2 inflammatory response. ILC2 numbers were significantly increased in lungs from exposed animals (1.66 +/- 0.19%) compared to controls (0.19 +/- 0.22%). Phosphorylation of the transactivation domain (Ser-468) of NF-kappa B in isolated ILC2 and IL-33 in lung epithelial cells were significantly increased (126.8 +/- 4.3% and 137 +/- 11% of controls respectively) by nano-TiO2 exposure. Lastly, radial endothelium-dependent arteriolar reactivity was significantly impaired (27 +/- 12%), while endothelium-independent dilation (7 +/- 14%) and -adrenergic sensitivity (8 +/- 2%) were not altered compared to control levels. Treatment with an anti- IL-33 antibody (1mg/kg) 30min prior to nano-TiO2 exposure resulted in a significant improvement in endothelium-dependent dilation and a decreased level of IL-33 in both plasma and bronchoalveolar lavage fluid. Conclusions: These results provide evidence that the uterine microvascular dysfunction that follows pulmonary ENM exposure may be initiated via activation of lung-resident ILC2 and subsequent systemic Th2-dependent inflammation.
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页数:13
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