House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation
House dust mite facilitates ovalbumin-specific allergic sensitization and airway inflammation
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DOI：
10.1164/rccm.200502-198oc
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发表时间：
2005-08-01
影响因子：
24.7
通讯作者：
Jordana, M
中科院分区：
文献类型：
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作者：
Fattouh, R;Pouladi, MA;Jordana, M
理由：过敏性气道疾病的小鼠模型极大地促进了我们对疾病诱导和发病机制的理解。尽管这些模型通常研究对单一抗原或过敏原的反应，但人类经常暴露于多种过敏原，每种过敏原都具有不同的抗原潜力。目的：鉴于气道暴露于卵清蛋白（OVA）（一种原型无害抗原）会诱导吸入耐受，我们希望研究如果 OVA 与屋尘螨提取物（HDM）同时遇到，这种反应会如何改变，我们最近表明，HDM 能够引发强烈的过敏性气道炎症反应，该反应至少部分由粒细胞巨噬细胞集落刺激因子介导。方法：Balb/c 小鼠每天暴露于 HDM（鼻内），然后立即暴露于雾化 OVA，持续 5 周。为了让 HDM 引起的炎症反应完全消退，让小鼠在不暴露的情况下休息 8 周，然后连续 3 天用雾化 OVA 重新激发。测量和主要结果：此时，我们观察到肺部存在强烈的嗜酸性粒细胞炎症反应，这与支气管高反应性的增加有关。此外，我们记录了 OVA 特异性 IgE 和 IgG(1) 的血清水平显着升高，并且用 OVA 体外刺激的脾细胞增加了 Th2 细胞因子白细胞介素 4 (IL-4)、IL-5 和 IL-13 的产生。结论：我们的数据表明，HDM 等强效过敏原有可能建立肺部微环境，从而促进对 OVA 等弱或无害抗原的过敏致敏的发展。
Rationale: Mouse models of allergic airway disease have greatly contributed to our understanding of disease induction and pathogenesis. Although these models typically investigate responses to a single antigen or allergen, humans are frequently exposed to a myriad of allergens, each with distinct antigenic potential. Objectives: Given that airway exposure to ovalbumin (OVA), a prototypic innocuous antigen, induces inhalation tolerance, we wished to investigate how this response would be altered if OVA were encountered concurrently with a house dust mite extract (HDM), which we have recently shown is capable of eliciting a robust allergic airway inflammatory response that is mediated, at least in part, by granulocyte-macrophage colony-stimulating factor. Methods: Balb/c mice were exposed daily to HDM (intranasally) followed immediately by exposure to aerosolized OVA for 5 weeks. To allow the inflammatory response elicited by HDM to subside fully, mice were then allowed to rest, unexposed, for 8 weeks, at which time they were rechallenged with aerosolized OVA for 3 consecutive days. Measurements and Main Results: At this time, we observed a robust eosinophilic inflammatory response in the lung that was associated with an increase in bronchial hyperreactivity. Moreover, we documented significantly elevated serum levels of OVA-specific IgE and IgG(1) and increased production of the Th2 cytokines interleukin 4 (IL-4), IL-5, and IL-13 by splenocytes stimulated in vitro with OVA. Conclusion: Our data demonstrate the potential of a potent allergen such as HDM to establish a lung microenvironment that fosters the development of allergic sensitization to otherwise weak or innocuous antigens, such as OVA.