PATHOGENESIS OF ASTHMA

描述：（改编自研究者摘要）：这是一项新应用 一个非常有经验的调查员建议检查亲属 嗜碱性粒细胞和T淋巴细胞在IL-4、IL-5产生中的作用 和IL-13在过敏性气道的启动和维持过程中 炎症细胞因子基因表达和蛋白质生产 支气管肺泡灌洗细胞和哮喘患者的支气管活检中， 在变应原攻击后的不同时间检查受试者。细胞 通过原位杂交确定每种细胞因子来源， 免疫组化，活组织检查，并通过流式细胞仪分析和功能研究 在BAL细胞中。研究人员假设，在接触过敏原后， 嗜碱性粒细胞迅速聚集到气道，是最初的主要来源。 IL-4和IL-13，而T淋巴细胞募集更慢， IL-5的主要来源。研究人员还假设， 所述细胞因子，组胺释放因子（HRF），在 哮喘通过激活浸润的嗜碱性粒细胞和嗜酸性粒细胞。因此他们 将评估HRF水平并确定气道后HRF的细胞位置 激发和急性和慢性哮喘发作。

DESCRIPTION: (Adapted from Investigator's abstract): This is a new application from a very experienced investigator that proposes to examine the relative contributions of basophils and T-lymphocytes in the production of IL-4, IL-5 and IL-13 during the initiation and maintenance of the allergic airway inflammation. Cytokine gene expression and protein production by bronchoalveolar lavage cells and in bronchial biopsies obtained from asthmatic subjects will be examined at varying times after allergen challenge. The cell source for each cytokine will be determined by in situ hybridization, immunohistochemistry in biopsies, and by FACS analysis and functional studies in BAL cells. The investigators hypothesize that after allergen exposure, basophils are recruited rapidly to the airways and are the initial major source of IL-4 and IL-13, while T lymphocytes are recruited more slowly and represent the major source of IL-5. The investigators also hypothesize that a newly described cytokine, histamine releasing factor (HRF), plays a central role in asthma by activating the infiltrating basophils and eosinophils. Therefore they will assess HRF levels and determine the cellular location of HRF after airway challenge and in acute and chronic asthmatic episodes.