Exposure of Brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation
Exposure of Brown Norway rats to diesel exhaust particles prior to ovalbumin (OVA) sensitization elicits IgE adjuvant activity but attenuates OVA-induced airway inflammation
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DOI：
10.1093/toxsci/kfi298
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发表时间：
2005-11-01
影响因子：
3.8
通讯作者：
Ma, JKH
中科院分区：
文献类型：
--
作者：
Dong, CC;Yin, XJJ;Ma, JKH
在人和动物模型中，在致敏过程中暴露于柴油废气颗粒物(DEP)已被证明增加抗原特异性IgE的产生并加重过敏性呼吸道炎症。在这项研究中，我们使用致敏后模型评估了短期DEP暴露对卵清蛋白(OVA)介导的反应的影响。棕色挪威大鼠首先暴露于过滤空气或DEP(20.6+/-2.7 mg/m(3))中，每天4h，连续5天。分别于末次空气或DEP暴露后第1天(第1天)，雾化吸入OVA(40.5+/-6.3 mg/m(3))致敏，第8天和第15天再次用OVA激发，第29天给予OVA激发，分别于第2次暴露后第9天、第30天和最后一次激发后24小时处死大鼠。对照组动物接受雾化生理盐水，而不是卵清蛋白。在第30天，DEP对抗原特异性IgE和Ig G的产生具有佐剂效应。在这两个时间点，单独接触DEP没有发现显著的呼吸道炎症反应和肺损伤。30d时，与空气+OVA染毒组相比，DEP组小鼠肺泡灌洗液(BAL)中无细胞乳酸脱氢酶活性、白蛋白含量及肺引流淋巴结T细胞数量及其CD4(+)、CD8(+)亚群均明显减少。DEP还能显著降低OVA诱导的BAL液中一氧化氮(NO)和肺泡巨噬细胞(AM)产生的NO、IL-10和IL-12。DEP或OVA单独给药后第9、30天AM和淋巴细胞内GSH含量均显著降低。DEP和OVA的联合暴露导致两种细胞中GSH的进一步耗竭。这些结果表明，在致敏前短期接触DEP对过敏原特异性IgE和Ig G产生的致敏作用有延迟作用，但对过敏原诱导的呼吸道炎症反应有减弱作用。
Exposure to diesel exhaust particles (DEP) during the sensitization process has been shown to increase antigen-specific IgE production and aggravate allergic airway inflammation in human and animal models. In this study, we evaluated the effect of short-term DEP exposure on ovalbumin (OVA)-mediated responses using a post-sensitization model. Brown Norway rats were first exposed to filtered air or DEP (20.6 +/- 2.7 mg/m(3)) for 4 h/day for five consecutive days. One day after the final air or DEP exposure (day 1), rats were sensitized with aerosolized OVA (40.5 +/- 6.3 mg/m(3)), and then again on days 8 and 15, challenged with OVA on day 29, and sacrificed on days 9 or 30, 24 h after the second OVA exposure or the final OVA challenge, respectively. Control animals received aerosolized saline instead of OVA. DEP were shown to elicit an adjuvant effect on the production of antigen-specific IgE and IgG on day 30. At both time points, no significant airway inflammatory responses and lung injury were found for DEP exposure alone. However, the OVA-induced inflammatory cell infiltration, acellular lactate dehydrogenase activity and albumin content in bronchoalveolar lavage (BAL) fluid, and numbers of T cells and their CD4(+) and CD8(+) subsets in lung-draining lymph nodes were markedly reduced by DEP on day 30 compared with the air-plus-OVA exposure group. The OVA-induced nitric oxide (NO) in the BAL fluid and production of NO, interleukin (IL)-10, and IL-12 by alveolar macrophages (AM) were also significantly lowered by DEP on day 30 as well as day 9. DEP or OVA alone decreased intracellular glutathione (GSH) in AM and lymphocytes on days 9 and 30. The combined DEP and OVA exposure resulted in further depletion of GSH in both cell types. These results show that short-term DEP exposure prior to sensitization had a delayed effect on enhancement of the sensitization in terms of allergen-specific IgE and IgG production, but caused an attenuation of the allergen-induced airway inflammatory responses.