Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice.
Engineered silica nanoparticles act as adjuvants to enhance allergic airway disease in mice.
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DOI：
10.1186/1743-8977-10-26
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发表时间：
2013-07-01
影响因子：
10
通讯作者：
Harkema JR
中科院分区：
文献类型：
--
作者：
Brandenberger C;Rowley NL;Jackson-Humbles DN;Zhang Q;Bramble LA;Lewandowski RP;Wagner JG;Chen W;Kaplan BL;Kaminski NE;Baker GL;Worden RM;Harkema JR
随着工程纳米颗粒（NP; ≤ 100 nm）的生产和使用的增加，对职业或环境NP暴露的潜在健康影响的安全性担忧已经上升。动物毒理学研究结果表明，吸入NP可能会导致肺损伤，随后出现急性或慢性炎症。患有哮喘或过敏性鼻炎等慢性呼吸道疾病的人可能更容易受到吸入NP的毒性作用。然而，很少有研究调查吸入NP的副作用，可能会增加过敏性气道疾病的发展。我们研究了聚乙二醇包被的无定形二氧化硅NP（SNP; 90 nm直径）在致敏过程中与过敏原共暴露时促进过敏性气道疾病的潜力。BALB/c小鼠通过鼻内滴注0.02%卵清蛋白（OVA;过敏原）或盐水（对照）致敏，并共暴露于0、10、100或400 μg SNP。然后在致敏后14和15天用0.5%OVA鼻内攻击OVA致敏小鼠，并在最后一次OVA攻击后一天处死所有动物。收集血液和支气管肺泡灌洗液（BALF），并对肺组织进行组织病理学、生化和分子分析。在OVA致敏过程中共暴露于SNP导致单独用OVA激发后过敏性气道疾病的剂量依赖性增强。与对不含SNP的OVA致敏的小鼠相比，这种促炎样作用表现为显著更高的OVA特异性血清IgE、气道嗜酸性粒细胞浸润、粘液细胞化生以及Th 2和Th 17细胞因子基因和蛋白表达。在生理盐水对照组中，SNP暴露在最高剂量下确实导致气道中性粒细胞中度增加。这些结果表明，气道暴露于工程SNP可以增强过敏原致敏性，并在二次过敏原暴露后促进过敏性气道疾病的更大表现。而SNP在高剂量下引起非过敏性小鼠的先天免疫应答，SNP的佐剂效应在低剂量下在过敏性小鼠中被发现，并且与Th 2/Th 17相关。总之，这些在小鼠中的发现表明，由于SNP的促排剂样性质，暴露于SNP的个体可能更容易表现出过敏性气道疾病。
With the increase in production and use of engineered nanoparticles (NP; ≤ 100 nm), safety concerns have risen about the potential health effects of occupational or environmental NP exposure. Results of animal toxicology studies suggest that inhalation of NP may cause pulmonary injury with subsequent acute or chronic inflammation. People with chronic respiratory diseases like asthma or allergic rhinitis may be even more susceptible to toxic effects of inhaled NP. Few studies, however, have investigated adverse effects of inhaled NP that may enhance the development of allergic airway disease. We investigated the potential of polyethylene glycol coated amorphous silica NP (SNP; 90 nm diameter) to promote allergic airway disease when co-exposed during sensitization with an allergen. BALB/c mice were sensitized by intranasal instillation with 0.02% ovalbumin (OVA; allergen) or saline (control), and co-exposed to 0, 10, 100, or 400 μg of SNP. OVA-sensitized mice were then challenged intranasally with 0.5% OVA 14 and 15 days after sensitization, and all animals were sacrificed a day after the last OVA challenge. Blood and bronchoalveolar lavage fluid (BALF) were collected, and pulmonary tissue was processed for histopathology and biochemical and molecular analyses. Co-exposure to SNP during OVA sensitization caused a dose-dependent enhancement of allergic airway disease upon challenge with OVA alone. This adjuvant-like effect was manifested by significantly greater OVA-specific serum IgE, airway eosinophil infiltration, mucous cell metaplasia, and Th2 and Th17 cytokine gene and protein expression, as compared to mice that were sensitized to OVA without SNP. In saline controls, SNP exposure did cause a moderate increase in airway neutrophils at the highest doses. These results suggest that airway exposure to engineered SNP could enhance allergen sensitization and foster greater manifestation of allergic airway disease upon secondary allergen exposures. Whereas SNP caused innate immune responses at high doses in non-allergic mice, the adjuvant effects of SNP were found at lower doses in allergic mice and were Th2/Th17 related. In conclusion, these findings in mice suggest that individuals exposed to SNP might be more prone to manifest allergic airway disease, due to adjuvant-like properties of SNP.
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纳米二氧化硅对卵清蛋白免疫大鼠肺功能的不良影响。
影响因子：
3.7
作者：
Han B;Guo J;Abrahaley T;Qin L;Wang L;Zheng Y;Li B;Liu D;Yao H;Yang J;Li C;Xi Z;Yang X
通讯作者：
Yang X
DOI：
10.4049/jimmunol.1100500
发表时间：
2011-07-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Ather JL;Ckless K;Martin R;Foley KL;Suratt BT;Boyson JE;Fitzgerald KA;Flavell RA;Eisenbarth SC;Poynter ME
通讯作者：
Poynter ME
影响因子：
4.9
作者：
Chang, J.;Delfino, R. J.;Cooper, D.
通讯作者：
Cooper, D.
影响因子：
6
作者：
Herbert, Cristan;Scott, Melissa M.;Kumar, Rakesh K.
通讯作者：
Kumar, Rakesh K.
影响因子：
3.4
作者：
Calvo, Florence Quesada;Fillet, Marianne;Cataldo, Didier
通讯作者：
Cataldo, Didier