Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, NC 27711, USA.
J Immunotoxicol. 2010 Mar;7(1):57-67. doi: 10.3109/15476910903373440.
Evidence suggests that the predisposition towards atopy begins early in life. Maternal allergy has been associated with an increased risk of the development of allergic disease in offspring. Some studies suggest that the development of childhood atopy may also be influenced by prenatal allergen exposure. In this study, a respiratory allergen exposure model was used to determine the impact of maternal sensitization (with or without additional exposures during pregnancy) on subsequent pup responses to homologous or heterologous allergen. Female BALB/c mice received two intratracheal aspiration (IA) exposures to Metarhizium anisopliae crude antigen (MACA) or Hank's buffered salt solution (HBSS) prior to breeding. Some mice also received three additional exposures during pregnancy. Control mothers did not receive treatment. Young adult offspring received three IA exposures to MACA, house dust mite extract (HDM) or HBSS. Offspring sensitized as young adults to either HDM or MACA developed an airway inflammatory response, including increased bronchoalveolar lavage fluid lactate dehydrogenase activity, total protein and total and differential cell counts compared to offspring exposed to HBSS. Increased airway responsiveness to methacholine was observed in pups treated with HDM but not with MACA. Maternal sensitization status (with or without gestational allergen exposure) had no effect on offspring response to either MACA or HDM. In conclusion, this study demonstrates that IA administration of MACA or HDM extract to young adult BALB/c mice induces the development of an inflammatory airway response. In contrast to previous reports, neither maternal sensitization nor gestational allergen exposure could be demonstrated to have a clear effect on offspring sensitization. This discrepancy may be a function of the respiratory sensitization and exposure protocol used in this study, which mimics natural sensitization more closely than do parenteral routes of exposure.
有证据表明，特应性倾向在生命早期就开始了。母体过敏与后代发生过敏性疾病的风险增加有关。一些研究表明，儿童特应性的发展也可能受到产前过敏原暴露的影响。在这项研究中，使用呼吸过敏原暴露模型来确定母体致敏（是否在怀孕期间进行额外暴露）对随后幼崽对同源或异源过敏原的反应的影响。雌性 BALB/c 小鼠在繁殖前接受两次气管内吸入（IA）Metarhizium anisopliae 粗抗原（MACA）或 Hank 的缓冲盐溶液（HBSS）暴露。一些小鼠在怀孕期间还接受了三次额外暴露。对照母亲未接受治疗。成年幼崽接受了三次 IA 暴露于 MACA、屋尘螨提取物（HDM）或 HBSS。成年幼崽对 HDM 或 MACA 致敏后会发展为气道炎症反应，包括支气管肺泡灌洗液乳酸脱氢酶活性、总蛋白和总细胞计数以及差异细胞计数增加，与暴露于 HBSS 的幼崽相比。在接受 HDM 治疗的幼崽中观察到对乙酰甲胆碱的气道反应性增加，但在接受 MACA 治疗的幼崽中未观察到。母体致敏状态（是否在怀孕期间接触过敏原）对幼崽对 MACA 或 HDM 的反应均无影响。总之，这项研究表明，IA 给予 MACA 或 HDM 提取物给成年 BALB/c 小鼠会诱导炎症性气道反应的发展。与之前的报告相反，母体致敏或妊娠期过敏原暴露都不能被证明对后代致敏有明显影响。这种差异可能是由于本研究中使用的呼吸致敏和暴露方案的功能，该方案比注射途径的暴露更能模拟自然致敏。
