Norris Reinero Carol R, Decile Kendra C, Berghaus Roy D, Williams Kurt J, Leutenegger Christian M, Walby William F, Schelegle Edward S, Hyde Dallas M, Gershwin Laurel J
Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California, Davis, California, USA.
Int Arch Allergy Immunol. 2004 Oct;135(2):117-31. doi: 10.1159/000080654. Epub 2004 Sep 2.
Animal models are used to mimic human asthma, however, not all models replicate the major characteristics of the human disease. Spontaneous development of asthma with hallmark features similar to humans has been documented to occur with relative frequency in only one animal species, the cat. We hypothesized that we could develop an experimental model of feline asthma using clinically relevant aeroallergens identified from cases of naturally developing feline asthma, and characterize immunologic, physiologic, and pathologic changes over 1 year.
House dust mite (HDMA) and Bermuda grass (BGA) allergen were selected by screening 10 privately owned pet cats with spontaneous asthma using a serum allergen-specific IgE ELISA. Parenteral sensitization and aerosol challenges were used to replicate the naturally developing disease in research cats. The asthmatic phenotype was characterized using intradermal skin testing, serum allergen-specific IgE ELISA, serum and bronchoalveolar lavage fluid (BALF) IgG and IgA ELISAs, airway hyperresponsiveness testing, BALF cytology, cytokine profiles using TaqMan PCR, and histopathologic evaluation.
Sensitization with HDMA or BGA in cats led to allergen-specific IgE production, allergen-specific serum and BALF IgG and IgA production, airway hyperreactivity, airway eosinophilia, an acute T helper 2 cytokine profile in peripheral blood mononuclear cells and BALF cells, and histologic evidence of airway remodeling.
Using clinically relevant aeroallergens to sensitize and challenge the cat provides an additional animal model to study the immunopathophysiologic mechanisms of allergic asthma. Chronic exposure to allergen in the cat leads to a variety of immunologic, physiologic, and pathologic changes that mimic the features seen in human asthma.
动物模型用于模拟人类哮喘，然而，并非所有模型都能复制人类疾病的主要特征。据记载，只有一种动物——猫，会相对频繁地自发出现具有与人类相似标志性特征的哮喘。我们推测，我们可以利用从自然发生的猫哮喘病例中鉴定出的具有临床相关性的气传变应原，开发一种猫哮喘实验模型，并描述1年内的免疫、生理和病理变化。
通过使用血清变应原特异性IgE ELISA对10只患有自发性哮喘的家养宠物猫进行筛查，选择屋尘螨（HDMA）和百慕大草（BGA）变应原。采用皮下致敏和气溶胶激发来在研究猫中复制自然发生的疾病。使用皮内皮肤试验、血清变应原特异性IgE ELISA、血清和支气管肺泡灌洗液（BALF）IgG和IgA ELISA、气道高反应性测试、BALF细胞学检查、使用TaqMan PCR的细胞因子谱分析以及组织病理学评估来表征哮喘表型。
猫用HDMA或BGA致敏导致变应原特异性IgE产生、变应原特异性血清和BALF IgG和IgA产生、气道高反应性、气道嗜酸性粒细胞增多、外周血单个核细胞和BALF细胞中的急性辅助性T细胞2型细胞因子谱，以及气道重塑的组织学证据。
使用具有临床相关性的气传变应原对猫进行致敏和激发，为研究过敏性哮喘的免疫病理生理机制提供了另一种动物模型。猫长期暴露于变应原会导致多种免疫、生理和病理变化，这些变化与人类哮喘中所见的特征相似。
