Department of Environmental Immunology, UFZ-Helmholtz Centre for Environmental Research Leipzig-Halle, Leipzig, Germany.
Allergy. 2013 Apr;68(4):481-9. doi: 10.1111/all.12121. Epub 2013 Feb 15.
One of the most promising strategies to face the increasing asthma prevalence and to prevent disease development might be an early contact with microbial compounds. However, little is known about an interaction between an early-life contact to microbial compounds leading to asthma protection in the offspring and a co-exposure to allergy-promoting pollutants.
Pregnant BALB/c mice were repeatedly exposed to aerosolized endotoxin (lipopolysaccharide, LPS). The offspring was further exposed to aerosolized LPS before allergen sensitization with ovalbumin (OVA). Some of the mice were co-exposed to mycotoxins or diesel exhaust particles (DEP) during pregnancy. The 6-week-old offspring was immunized with OVA and analyzed in a murine asthma model.
While the offspring of naïve mothers developed an asthma-like phenotype, the offspring of mice perinatally exposed to LPS was significantly protected. Co-exposure of mice to mycotoxins or DEP during pregnancy inhibited the LPS-induced protection leading to the development of eosinophilic airway inflammation, airway hyperactivity, and increased antigen-specific IgE levels in the offspring. Furthermore, the asthma-preventive effect of perinatal LPS exposure was IFN-gamma dependent. Additionally, the IFN-gamma promoter of CD4+ T cells in the LPS-exposed offspring revealed a significant protection against loss of histone 4 acetylation, which was abolished after prenatal co-exposure to pollutants. Prenatal treatment of mice with the antioxidant N-acetylcysteine reversed the pollutant-induced increased asthma risk in the offspring.
Our results show that exposure to pollutants during pregnancy may cause the development of allergic asthma in the offspring by inhibiting the endotoxin-induced perinatal asthma protection.
应对哮喘发病率不断上升并预防疾病发展的最有希望的策略之一可能是尽早接触微生物化合物。然而，人们对早期接触微生物化合物导致后代哮喘保护作用，以及与促进过敏的污染物同时暴露之间的相互作用知之甚少。
反复用气溶胶形式给怀孕的 BALB/c 小鼠内毒素（脂多糖，LPS）。在卵清蛋白（OVA）致敏前，进一步使子代为气溶胶 LPS 暴露。一些妊娠期间的小鼠同时接触霉菌毒素或柴油机排气颗粒（DEP）。用 OVA 免疫 6 周龄的后代，并在小鼠哮喘模型中进行分析。
尽管未暴露的母亲的后代发展出类似哮喘的表型，但 LPS 围产期暴露的小鼠的后代则受到明显保护。妊娠期间同时暴露于霉菌毒素或 DEP 会抑制 LPS 诱导的保护作用，导致子代发生嗜酸性气道炎症、气道高反应性和抗原特异性 IgE 水平升高。此外，围产期 LPS 暴露的哮喘预防作用依赖于 IFN-γ。此外，LPS 暴露后代的 CD4+T 细胞 IFN-γ启动子对组蛋白 4 乙酰化的丧失具有明显的保护作用，而产前同时暴露于污染物则会消除这种保护作用。用抗氧化剂 N-乙酰半胱氨酸对小鼠进行产前治疗可逆转污染物对子代哮喘风险的增加。
我们的结果表明，妊娠期间暴露于污染物可能通过抑制内毒素诱导的围产期哮喘保护作用，导致后代发生过敏性哮喘。
