Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma
Prenatal lipopolysaccharide-exposure prevents allergic sensitization and airway inflammation, but not airway responsiveness in a murine model of experimental asthma
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DOI：
10.1111/j.1365-2222.2005.02184.x
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发表时间：
2005-03-01
影响因子：
6.1
通讯作者：
Renz, H
中科院分区：
文献类型：
--
作者：
Blümer, N;Herz, U;Renz, H
背景流行病学证据强调产前环境因素对产后过敏发生的影响。在这方面，已经发现脂多糖（LPS）暴露与儿童过敏的发生之间存在负相关。 目的 在实验性哮喘小鼠模型中评估产前 LPS 暴露对产后呼吸道过敏发生的影响。 方法 雌性 BALB/c 小鼠在受孕前和妊娠期间暴露于 LPS。出生几周后，后代对卵清蛋白 (OVA) 敏感，随后进行气溶胶过敏原激发。结果 产前、母体 LPS 暴露增强了新生儿 IFN-γ 的产生，但不增强 IL-4 和 IL-2 的产生。产前暴露于 LPS 的小鼠的 OVA 致敏伴随着抗 OVA IgG1 和 IgE 以及未改变的 IgG2a 抗体反应的显着抑制，同时伴随着脾白细胞促有丝分裂刺激后 IL-5 和 IL-13 水平的显着降低。对过敏原挑战后支气管肺泡灌洗液的评估显示，这些小鼠的嗜酸性粒细胞和巨噬细胞显着减少。令人惊讶的是，气道高反应性（支气管哮喘的标志）的发展并未受到影响。 结论 这项研究提供了第一个实验证据，表明 LPS 可能已经在产前发挥作用，以调节后代过敏的发展。
Background Epidemiological evidence underlines the impact of prenatal environmental factors on the development of postnatal allergies. In this regard an inverse correlation between lipopolysaccharide (LPS) exposure and development of childhood allergy has been found.Objective To assess the impact of prenatal LPS exposure on the development of postnatal respiratory allergies in a mouse model of experimental asthma.Methods Female BALB/c mice were exposed to LPS before conception and during pregnancy. Several weeks after birth offspring were sensitized to ovalbumin (OVA) followed by aerosol allergen challenges.Results Prenatal, maternal LPS-exposure enhanced neonatal IFN-gamma, but not IL-4 and IL-2 production. OVA sensitization of prenatally LPS-exposed mice was accompanied by a marked suppression in anti-OVA IgG1 and IgE as well as unchanged IgG2a antibody responses, paralleled by a significant reduction in IL-5 and IL-13 levels following mitogenic stimulation of splenic leucocytes. Assessment of bronchoalveolar lavage fluids following allergen challenges revealed a marked reduction in eosinophils and macrophages in these mice. Surprisingly, development of airway hyper-responsiveness, a hallmark of bronchial asthma, was not affected.Conclusion This study provides first experimental evidence that LPS may already operate in prenatal life in order to modulate the development of allergies in the offspring.