COCKROACH ALLERGEN INDUCED AIRWAY INFLAMMATION

尽管我们对这种机制的理解有了很大的提高 参与哮喘的病理、死亡率和发病率 继续上升，特别是在市中心的儿童中。许多疾病的病因 市中心哮喘患者似乎与蟑螂传播有关 过敏原。在目前的建议中，我们有详细的研究要评估 蟑螂变应原诱导的小鼠呼吸道模型的特异性机制 类似于人类哮喘特应性反应的高反应性。这个 在这个模型中，过敏反应包括显著增加的 过敏原特异性血清IgE，BAL中组胺的即时释放， 变应原特异性呼吸道嗜酸性粒细胞增多症和显著改变的呼吸道 与呼吸道炎症相关的生理学。具体关注点 这项提案中的研究将审查通过哪些机制 特异性趋化因子在不同阶段诱导呼吸道高反应性 蟑螂变应原引起的反应。差异化响应在 过敏性呼吸道疾病的某些阶段似乎集中在 变应原再激发时的炎症强度和 特异性趋化因子介导的局部白细胞群激活。我们 假设利用特定受体的特定CC趋化因子 将负责在不同的时间引起呼吸道高反应性 蟑螂变应原诱导的呼吸道反应的各个阶段。为了测试这一点 假设，本提案中概述的研究将检查两个CC 趋化因子家族，单核细胞趋化蛋白-1和嗜酸性粒细胞趋化因子，特异性结合CCR2和 CCR3，似乎介导了导致不同反应的不同反应 呼吸道高反应性。我们的研究内容包括：1) 表征炎症反应和趋化因子的表达谱 在过敏反应的不同阶段，2)检查 趋化因子耗竭后的炎症和气道生理学 趋化因子“敲除”(KO)在发育过程中对白细胞的影响 对过敏性呼吸道疾病的研究，4)确定特异性功能 CCR2和CCR3KO小鼠的趋化因子受体，以及5)阐明 单核细胞趋化蛋白-1和嗜酸性粒细胞趋化因子对特定白细胞群的激活作用 参与了过敏性呼吸道反应。这些思想的发展 将有助于阐明特定介体的机械活动 以及蟑螂变应原不同阶段的细胞群 呼吸道炎症加重，导致呼吸道高反应性 并帮助确定过敏症患者疾病进展的差异 气道口。

Despite a substantial increase in our understanding of the mechanism involved in the pathology of asthma, the mortality and morbidity rates continue to rise, especially in inner-city children. The etiology of many inner city asthmatics appears to be related to cockroach-delivered allergens. In the present proposal, we have detailed studies to assess specific mechanisms of a murine model of cockroach allergen-induced airway hyperreactivity which resemble atopic human asthmatics responses. The allergic responses in this model include significant increases in allergen-specific serum IgE, immediate release of histamine in the BAL, allergen-specific airway eosinophilia, and significantly altered airway physiology which correlates to the airway inflammation. The specific focus of the studies in this proposal will examine the mechanisms by which specific chemokines induce airway hyperreactivity at different stages of the cockroach allergen-induced responses. Differential responses at certain stages of allergic airway disease appears to center around the intensity of inflammation at the time of allergen rechallenge and the specific chemokine-mediated activation of local leukocyte populations. We hypothesize that specific CC chemokines which utilize specific receptors will be responsible for inducing airway hyperreactivity at different stages of cockroach allergen-induced airway responses. To test this postulate, the studies outlined in this proposal will examine two CC family chemokines, MCP-1 and eotaxin, which specifically bind to CCR2 and CCR3, respectively, and appear to mediate different responses leading to airway hyperreactivity. Our studies will include the following: 1) To characterize the inflammatory response and chemokine expression profiles at different stages of allergic response, 2) To examine the alteration of inflammation and airway physiology after depletion of the chemokines or in chemokine "knockout" (KO) on leukocyte populations during the development of allergic airway disease, 4) To determine the function of specific chemokine receptors in CCR2 and CCR3 KO mice, and 5) To elucidate the activational role of MCP-1 and eotaxin on specific leukocyte populations involved in the allergic airway responses. The development of these ideas will allow elucidation of the mechanistic activity of specific mediators and cell populations involved at different stages of cockroach allergen exacerbations of airway inflammation, leading to airway hyperreactivity and help define differences in disease progression within the allergic airway.