IMMUNOREGULATION OF THE CELLS AND MEDIATORS OF ASTHMA

这个哮喘、过敏和免疫疾病合作组织的目标是， 研究中心（AAIDCRC）计划在华盛顿大学是为了 明确哮喘气道炎症的基本病理生理机制 并确定控制这一过程的关键免疫调节信号 炎症过程。 这些研究将有助于设计和测试新的 治疗干预以改善或预防过敏性肺损伤。 变应原诱导花生四烯酸5-脂氧合酶产物的释放 代谢在早期和晚期的病理生理学中都是重要的。 晚期哮喘反应 研究将确定如何5- 在介导肺部炎症的细胞中调节脂氧合酶途径 以及5-脂氧合酶抑制剂对哮喘的影响 炎症反应。 T细胞源性细胞因子白细胞介素-4（IL-4） 和干扰素（IFN）-γ参与了诱导或 分别抑制CD 4 T细胞的Th 2亚群， 免疫球蛋白E抗体的B细胞，和生长和吸引组织的 肥大细胞和嗜酸性粒细胞。 该提案将讨论以下因素的因果作用： 这些T细胞细胞因子在产生肺过敏素质， 获得转基因小鼠，其差异仅在于它们的相对能力， 产生IL-4或IFN-γ以响应抗原攻击。 的 嗜酸性粒细胞特异性流入支气管组织是一个关键事件 晚期哮喘反应的发病机制。 拟定研究 将确定IL-4增强免疫应答的分子机制。 嗜酸性粒细胞对内皮细胞粘附分子的粘附， 抗粘连治疗在哮喘中的潜在疗效。哮喘发病率 在过去的十年里， 妇女和黑人处于特别危险的境地。 示范与教育 （D&E）研究项目将研究导致哮喘增加的因素 太平洋西北地区和美国妇女和少数民族的死亡率 D&E项目将侧重于遵守、教育和心理社会 青少年哮喘患者的适应问题 多学科方法 将在这些研究中使用。 调查人员有很强的 以前的高生产力的合作研究的历史与对方 他是过敏和免疫学、细胞免疫学、细胞免疫学等研究领域的专家， 分子生物学、生理学、形态学、心理学、医学 地理学和生物统计学，以解决这些基本问题， 哮喘的病理学

The goals of this Asthma and Allergic and Immunologic Diseases Cooperative Research Center (AAIDCRC) program at the University of Washington are to define basic pathophysiologic mechanisms of airway inflammation in asthma and determine the critical immunoregulatory signals controlling this inflammatory process. These studies will help design and test new therapeutic interventions to ameliorate or prevent allergic lung injury. Allergen-induced release of 5-lipoxygenase products of arachidonic acid metabolism is important in the pathophysiology of both early-phase and late-phase asthmatic responses. Studies will define how the 5- lipoxygenase pathway is regulated in cells which mediate lung inflammation in asthma and the effects of 5-lipoxygenase inhibition on these inflammatory reactions. The T cell-derived cytokines interleukin-4 (IL-4) and interferon (IFN)-gamma have been implicated in the induction or inhibition, respectively, of the Th2 subset of CD4 T cells, the production of IgE antibodies by B cells, and the growth and attraction to tissues of mast cells and eosinophils. This proposal will address the causal role of these T cell cytokines in producing a pulmonary allergic diathesis by deriving transgenic mice that differ only in their relative capacity to produce IL-4 or IFN-gamma in response to antigenic challenge. The specific influx of eosinophils into the bronchial tissues is a key event in the pathogenesis of late-phase asthmatic responses. Proposed studies will determine the molecular mechanisms by which IL-4 augments the adherence of eosinophils to endothelial cell adhesion molecules and the potential efficacy of antiadhesion treatment in asthma. Asthma morbidity and mortality have greatly increased in the U.S. over the past decade with women and Blacks at particular risk. The Demonstration and Education (D&E) Research Project will examine factors leading to increased asthma mortality in women and minorities in the Pacific Northwest and the U.S. The D&E project and will focus on compliance, education, and psychosocial adjustment issues in teenagers with asthma. A multidisciplinary approach will be employed in these studies. The investigators have a strong history of prior highly productive collaborative research with each other and are expert in the investigative areas of allergy and immunology, cell and molecular biology, physiology, morphology, psychology, medical geography, and biostatistics necessary to address these basic questions on the pathobiology of asthma.