Tournoy K G, Kips J C, Schou C, Pauwels R A
Department of Respiratory Diseases, University Hospital Gent, Gent, Belgium.
Clin Exp Allergy. 2000 Jan;30(1):79-85. doi: 10.1046/j.1365-2222.2000.00772.x.
House dust mites (HDMs) are the major source of perennial allergens causing human allergic asthma. Animal models mimicking as closely as possible the allergic features observed in human asthma are therefore interesting tools for studying the immunological and pathophysiological mechanisms involved. Especially the role of eosinophils and allergen-specific immunoglobulin (Ig) E in the pathophysiology of airway hyperresponsiveness (AHR) remains a subject of intense debate.
To develop a mouse model of allergic airway inflammation and hyperresponsiveness based on the use of purified house dust mite allergen (Der p 1) as clinical relevant allergen. Furthermore, we studied the effects of low dose allergen exposure on the airway eosinophilia and AHR.
On day 0, C57Bl/6 mice were immunized with purified Der p 1 intraperitoneally. From day 14-20, the mice were exposed daily to a 30-min aerosol of different concentrations of house dust mite extract.
Mice, actively immunized with Der p 1 and subsequently exposed to HDM aerosols, developed AHR, eosinophil infiltration of the airways and allergen-specific IgE. Moreover, lowering the concentration of the HDM aerosol also induced AHR and IgE without apparent eosinophil influx into the airways. Der p 1-sensitized mice exposed to PBS produced IgE, but did not show AHR or eosinophil influx.
This in vivo model of HDM-induced allergic airway changes suggests that AHR is not related to either eosinophil influx or allergen-specific serum IgE, thereby reducing the importance of these factors as essential elements for allergic AHR.
屋尘螨(HDM)是引起人类过敏性哮喘的常年性过敏原的主要来源。因此,尽可能紧密模拟人类哮喘中观察到的过敏特征的动物模型是研究相关免疫和病理生理机制的有趣工具。特别是嗜酸性粒细胞和过敏原特异性免疫球蛋白(Ig)E在气道高反应性(AHR)病理生理学中的作用仍然是激烈辩论的主题。
基于使用纯化的屋尘螨过敏原(Der p 1)作为临床相关过敏原,建立过敏性气道炎症和高反应性的小鼠模型。此外,我们研究了低剂量过敏原暴露对气道嗜酸性粒细胞增多和AHR的影响。
在第0天,将C57Bl/6小鼠腹腔内注射纯化的Der p 1进行免疫。从第14 - 20天,每天将小鼠暴露于不同浓度的屋尘螨提取物的30分钟气雾剂中。
用Der p 1主动免疫并随后暴露于HDM气雾剂的小鼠出现了AHR、气道嗜酸性粒细胞浸润和过敏原特异性IgE。此外,降低HDM气雾剂的浓度也诱导了AHR和IgE,而气道中没有明显的嗜酸性粒细胞流入。暴露于PBS的Der p 1致敏小鼠产生了IgE,但未显示出AHR或嗜酸性粒细胞流入。
这种HDM诱导的过敏性气道变化的体内模型表明,AHR与嗜酸性粒细胞流入或过敏原特异性血清IgE均无关,从而降低了这些因素作为过敏性AHR必需要素的重要性。