Departamento de Biointeração, Instituto de Ciências da Saúde, Universidade Federal da Bahia, Av, Reitor Miguel Calmon, Canela, Salvador, Bahia, CEP 40110902, Brasil.
Respir Res. 2010 May 1;11(1):51. doi: 10.1186/1465-9921-11-51.
The dust mite Blomia tropicalis is an important source of aeroallergens in tropical areas. Although a mouse model for B. tropicalis extract (BtE)-induced asthma has been described, no study comparing different mouse strains in this asthma model has been reported. The relevance and reproducibility of experimental animal models of allergy depends on the genetic background of the animal, the molecular composition of the allergen and the experimental protocol.
This work had two objectives. The first was to study the anti-B. tropicalis allergic responses in different mouse strains using a short-term model of respiratory allergy to BtE. This study included the comparison of the allergic responses elicited by BtE with those elicited by ovalbumin in mice of the strain that responded better to BtE sensitization. The second objective was to investigate whether the best responder mouse strain could be used in an experimental model of allergy employing relatively low BtE doses.
Groups of mice of four different syngeneic strains were sensitized subcutaneously with 100 microg of BtE on days 0 and 7 and challenged four times intranasally, at days 8, 10, 12, and 14, with 10 microg of BtE. A/J mice, that were the best responders to BtE sensitization, were used to compare the B. tropicalis-specific asthma experimental model with the conventional experimental model of ovalbumin (OVA)-specific asthma. A/J mice were also sensitized with a lower dose of BtE.
Mice of all strains had lung inflammatory-cell infiltration and increased levels of anti-BtE IgE antibodies, but these responses were significantly more intense in A/J mice than in CBA/J, BALB/c or C57BL/6J mice. Immunization of A/J mice with BtE induced a more intense airway eosinophil influx, higher levels of total IgE, similar airway hyperreactivity to methacholine but less intense mucous production, and lower levels of specific IgE, IgG1 and IgG2 antibodies than sensitization with OVA. Finally, immunization with a relatively low BtE dose (10 microg per subcutaneous injection per mouse) was able to sensitize A/J mice, which were the best responders to high-dose BtE immunization, for the development of allergy-associated immune and lung inflammatory responses.
The described short-term model of BtE-induced allergic lung disease is reproducible in different syngeneic mouse strains, and mice of the A/J strain was the most responsive to it. In addition, it was shown that OVA and BtE induce quantitatively different immune responses in A/J mice and that the experimental model can be set up with low amounts of BtE.
热带尘螨是热带地区重要的空气过敏原来源。虽然已经描述了用于尘螨提取物(BtE)诱导哮喘的小鼠模型,但尚无关于该哮喘模型中不同小鼠品系的比较研究。过敏实验动物模型的相关性和可重复性取决于动物的遗传背景、过敏原的分子组成和实验方案。
本工作有两个目的。第一个目的是使用 BtE 诱导的短期呼吸过敏模型研究不同小鼠品系对 Blomia tropicalis 的过敏反应。该研究包括比较 BtE 诱导的过敏反应与卵清蛋白(OVA)诱导的过敏反应在对 BtE 致敏反应最佳的小鼠中的差异。第二个目的是研究最佳反应小鼠品系是否可用于相对低剂量 BtE 的过敏实验模型。
4 种同基因品系的小鼠分别在第 0 天和第 7 天经皮接受 100μg 的 BtE 致敏,并在第 8、10、12 和 14 天经鼻内给予 10μg 的 BtE 进行 4 次激发。A/J 小鼠对 BtE 致敏反应最佳,用于比较尘螨特异性哮喘实验模型与传统的 OVA 特异性哮喘实验模型。A/J 小鼠也用较低剂量的 BtE 致敏。
所有品系的小鼠均有肺部炎症细胞浸润和抗 BtE IgE 抗体水平升高,但 A/J 小鼠的反应明显强于 CBA/J、BALB/c 或 C57BL/6J 小鼠。用 BtE 免疫 A/J 小鼠诱导了更强烈的气道嗜酸性粒细胞浸润、更高水平的总 IgE、对乙酰甲胆碱的气道高反应性相似,但粘液产生较少、特异性 IgE、IgG1 和 IgG2 抗体水平较低,而用 OVA 免疫则没有这些情况。最后,用相对低剂量(每只小鼠皮下注射 10μg)的 BtE 免疫可使对高剂量 BtE 免疫反应最佳的 A/J 小鼠致敏,引发与过敏相关的免疫和肺部炎症反应。
所描述的 BtE 诱导的过敏性肺部疾病短期模型在不同的同基因小鼠品系中具有可重复性,且 A/J 品系对其反应最为敏感。此外,研究表明 OVA 和 BtE 在 A/J 小鼠中诱导了不同数量的免疫反应,且该实验模型可以用低剂量的 BtE 建立。