Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model
Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model
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DOI：
10.1093/toxsci/kfi255
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发表时间：
2005-10-01
影响因子：
3.8
通讯作者：
Pieters, R
中科院分区：
文献类型：
--
作者：
de Haar, C;Hassing, I;Pieters, R
为了更深入地了解颗粒物质（PM）诱导佐剂活性的机制，我们研究了超细炭黑颗粒（CBP）对气道毒性/炎症和卵清蛋白（OVA）过敏致敏的动力学。小鼠鼻内单独暴露于OVA或与不同浓度的CBP联合暴露。在第4天和第8天评估气道毒性和炎症。第8天观察肺引流支气管周围淋巴结（PBLN）免疫佐剂的作用。在第21天和第28天测量抗原特异性IgE，而在OVA攻击后（第28天）研究过敏性气道炎症。结果显示，CBP总剂量为200 μ g /只小鼠，而不是20 μ g或2 μ g /只小鼠，可引起立即气道炎症。这200 μ g CBP是唯一具有免疫佐剂活性的剂量，通过诱导PBLN的扩大和增加ova特异性Th2细胞因子（IL-4、IL-5和IL-10）的产生。进一步检测200 μ g CBP给药后的免疫佐剂活性。然而，第21天血清中OVA特异性IgE水平升高证实了全身性致敏，这进一步得到了OVA挑战后过敏性气道炎症的支持。我们的数据显示早期气道毒性与CBP的辅助作用之间存在联系。此外，结果表明，暴露于CBP后早期局部细胞因子的产生可预测过敏性气道炎症。此外，该模型适合于研究颗粒佐剂活性在气道毒性、炎症等机制中的作用，以及预测不同颗粒的佐剂潜能。
To gain more insight into the mechanisms of particulate matter (PM)-induced adjuvant activity, we studied the kinetics of airway toxicity/inflammation and allergic sensitization to ovalbumin (OVA) in response to ultrafine carbon black particles (CBP). Mice were exposed intranasally to OVA alone or in combination with different concentrations of CBP. Airway toxicity and inflammation were assessed at days 4 and 8. Immune adjuvant effects were studied in the lung draining peribronchial lymph nodes (PBLN) at day 8. Antigen-specific IgE was measured at days 21 and 28, whereas allergic airway inflammation was studied after OVA challenges (day 28). Results show that a total dose of 200 mu g CBP per mouse, but not 20 mu g or 2 mu g, induced immediate airway inflammation. This 200 mu g CBP was the only dose that had immune adjuvant activity, by inducing enlargement of the PBLN and increasing OVA-specific production of Th2 cytokines (IL-4, IL-5, and IL-10). The immune adjuvant activity of 200 mu g CBP dosing was further examined. Whereas increased OVA-specific IgE levels in serum on day 21 confirms systemic sensitization, this was further supported by allergic airway inflammation after challenges with OVA. Our data show a link between early airway toxicity and adjuvant effects of CBP. In addition, results indicate that local cytokine production early after exposure to CBP is predictive of allergic airway inflammation. In addition this model appears suitable for studying the role of airway toxicity, inflammation and other mechanisms of particle adjuvant activity, and predicting the adjuvant potential of different particles.