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超细炭黑颗粒可引发早期气道炎症,并在小鼠过敏性气道疾病模型中具有佐剂活性。

Ultrafine carbon black particles cause early airway inflammation and have adjuvant activity in a mouse allergic airway disease model.

作者信息

de Haar Colin, Hassing Ine, Bol Marianne, Bleumink Rob, Pieters Raymond

机构信息

Department of Immunotoxicology, Institute for Risk Assessment Sciences, Utrecht University, The Netherlands.

出版信息

Toxicol Sci. 2005 Oct;87(2):409-18. doi: 10.1093/toxsci/kfi255. Epub 2005 Jul 13.

Abstract

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 microg CBP per mouse, but not 20 microg or 2 microg, induced immediate airway inflammation. This 200 microg 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 microg 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.

摘要

为了更深入了解颗粒物(PM)诱导的佐剂活性机制,我们研究了超细炭黑颗粒(CBP)引发的气道毒性/炎症动力学以及对卵清蛋白(OVA)的过敏致敏作用。将小鼠经鼻暴露于单独的OVA或与不同浓度CBP联合的OVA中。在第4天和第8天评估气道毒性和炎症。在第8天研究肺引流支气管周围淋巴结(PBLN)中的免疫佐剂效应。在第21天和第28天测量抗原特异性IgE,而在OVA激发后(第28天)研究过敏性气道炎症。结果显示,每只小鼠200微克CBP的总剂量可诱导即刻气道炎症,而20微克或2微克则不能。这200微克CBP是唯一具有免疫佐剂活性的剂量,它可诱导PBLN增大并增加OVA特异性Th2细胞因子(IL-4、IL-5和IL-10)的产生。进一步研究了200微克CBP给药的免疫佐剂活性。第21天血清中OVA特异性IgE水平升高证实了全身致敏,OVA激发后的过敏性气道炎症进一步支持了这一点。我们的数据显示了早期气道毒性与CBP佐剂效应之间的联系。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,该模型似乎适用于研究气道毒性、炎症和颗粒佐剂活性的其他机制的作用,并预测不同颗粒的佐剂潜力。

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