Murine Model of Allergen Induced Asthma
Murine Model of Allergen Induced Asthma
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DOI：
10.3791/3771
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发表时间：
2012-05-01
影响因子：
1.2
通讯作者：
Reddy, Raju C.
中科院分区：
文献类型：
--
作者：
Reddy, Aravind T.;Lakshmi, Sowmya P.;Reddy, Raju C.
哮喘是导致发病率和死亡率的主要原因，影响着全世界约3亿人。(1)超过8%的美国人口患有哮喘，发病率还在上升。(2)与其他疾病一样，过敏性呼吸道疾病的动物模型极大地促进了对潜在病理生理学的了解，有助于确定潜在的治疗靶点，并允许对可能的新疗法进行临床前测试。过敏性呼吸道疾病的模型已经在几个动物物种中开发出来，但小鼠模型特别吸引人，因为这些动物的低成本、现成的可获得性和良好的免疫系统。(3)各种转基因菌株的可获得性进一步增加了这些模型的吸引力。(4)这里我们描述了两种以卵清蛋白为抗原的过敏性呼吸道疾病小鼠模型。在最初通过腹腔注射致敏之后，一个模型通过雾化吸入提供抗原挑战，另一个模型通过气管内传递。这两种模型优势互补，各自模仿人类哮喘的主要特征。(5)急性哮喘的主要特征包括对乙酰甲胆碱(AHR)和富含嗜酸性粒细胞的呼吸道炎症等刺激的过度呼吸道反应。这些也是过敏原挑战在我们的小鼠模型中的显著影响，(5，6)，我们描述了测量它们的技术，从而评估实验操作的效果。具体地说，我们描述了测量呼吸道高反应性的侵入性和非侵入性技术，以及评估炎症细胞渗入呼吸道和肺的方法。通过支气管肺泡灌洗收集呼吸道炎症细胞，而肺组织病理学用于评估整个器官的炎症标志物。这些技术为研究哮喘提供了强大的工具，而这种方法在人类身上是不可能的。
Asthma is a major cause of morbidity and mortality, affecting some 300 million people throughout the world.(1) More than 8% of the US population has asthma, with the prevalence increasing.(2) As with other diseases, animal models of allergic airway disease greatly facilitate understanding of the underlying pathophysiology, help identify potential therapeutic targets, and allow preclinical testing of possible new therapies. Models of allergic airway disease have been developed in several animal species, but murine models are particularly attractive due to the low cost, ready availability, and well-characterized immune systems of these animals.(3) Availability of a variety of transgenic strains further increases the attractiveness of these models.(4) Here we describe two murine models of allergic airway disease, both employing ovalbumin as the antigen. Following initial sensitization by intraperitoneal injection, one model delivers the antigen challenge by nebulization, the other by intratracheal delivery. These two models offer complementary advantages, with each mimicking the major features of human asthma.(5)The major features of acute asthma include an exaggerated airway response to stimuli such as methacholine (airway hyperresponsiveness; AHR) and eosinophil-rich airway inflammation. These are also prominent effects of allergen challenge in our murine models,(5,6) and we describe techniques for measuring them and thus evaluating the effects of experimental manipulation. Specifically, we describe both invasive(7) and noninvasive(8) techniques for measuring airway hyperresponsiveness as well as methods for assessing infiltration of inflammatory cells into the airways and the lung. Airway inflammatory cells are collected by bronchoalveolar lavage while lung histopathology is used to assess markers of inflammation throughout the organ. These techniques provide powerful tools for studying asthma in ways that would not be possible in humans.