婴儿哮喘小鼠模型中过敏性气道炎症的特征
Characteristic features of allergic airway inflammation in a murine model of infantile asthma.
作者信息
Ohki Yasushi, Tokuyama Kenichi, Mayuzumi Hiroo, Sato Akira, Koyama Harumi, Takizawa Takumi, Arakawa Hirokazu, Mochizuki Hiroyuki, Morikawa Akihiro
机构信息
Department of Pediatrics and Developmental Medicine, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
出版信息
Int Arch Allergy Immunol. 2005 Sep;138(1):51-8. doi: 10.1159/000087357. Epub 2005 Aug 9.
BACKGROUND
The pathophysiology of infantile asthma may differ from that in older children or in adults, partly because of the different immune response depending upon maturation. In adult mice, the sensitizing dose of antigen is known to be critical to the polarized development of helper T cell subsets and allergic airway inflammation. We wanted to know the characteristics of allergic airway inflammation of infantile asthma by developing a murine model.
METHODS
BALB/C mice at different stages of maturation (juvenile: 3 days after birth; adult: 8 weeks of age) were sensitized with 10 or 1,000 microg ovalbumin (OVA) or vehicle. The animals were then challenged with aerosolized OVA or saline once a day during 6 consecutive days. After the final challenge, bronchial hyperresponsiveness (BHR), bronchoalveolar lavage fluid (BALF), histological changes in the airways and immunological status were examined.
RESULTS
In both juvenile and adult animals, sensitization with 10 microg OVA induced the T helper 2 response (elevated IL-4 and decreased IFN-gamma levels). BHR, airway eosinophilia, the inflammatory cell infiltration, goblet cell metaplasia (GCM), and IgE antibody production were more prominent in animals given this dose than 1,000 microg OVA. Among these responses, GCM as well as BALF IL-4, and BHR were comparable between juvenile and adult animals, whereas other parameters were lower in juvenile animals, especially in those given 1,000 microg OVA.
CONCLUSION
GCM and, consequently, airway mucus hypersecretion may be an important component of allergic airway inflammation in infantile asthma.
背景
婴幼儿哮喘的病理生理学可能与大龄儿童或成人不同,部分原因是由于免疫反应因成熟度而异。在成年小鼠中,已知抗原的致敏剂量对辅助性T细胞亚群的极化发育和过敏性气道炎症至关重要。我们希望通过建立小鼠模型来了解婴幼儿哮喘过敏性气道炎症的特征。
方法
用10或1000微克卵清蛋白(OVA)或赋形剂对不同成熟阶段的BALB/C小鼠(幼年:出生后3天;成年:8周龄)进行致敏。然后在连续6天内每天用雾化的OVA或生理盐水对动物进行激发。末次激发后,检测支气管高反应性(BHR)、支气管肺泡灌洗液(BALF)、气道组织学变化和免疫状态。
结果
在幼年和成年动物中,用10微克OVA致敏均诱导了辅助性T细胞2型反应(白细胞介素-4升高和干扰素-γ水平降低)。给予该剂量的动物,其BHR、气道嗜酸性粒细胞增多、炎性细胞浸润、杯状细胞化生(GCM)和IgE抗体产生比给予1000微克OVA的动物更明显。在这些反应中,幼年和成年动物的GCM以及BALF白细胞介素-4和BHR相当,而幼年动物的其他参数较低,尤其是给予1000微克OVA的动物。
结论
GCM以及由此导致的气道黏液分泌过多可能是婴幼儿哮喘过敏性气道炎症的重要组成部分。