PATHOGENESIS OF ASTHMA

描述：(改编自调查者摘要)：这是一个新的应用程序 从一位非常有经验的调查员那里建议检查亲属 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在变态反应性呼吸道的启动和维持中的作用 发炎。细胞因子基因表达和蛋白质合成 哮喘患者的支气管肺泡灌洗细胞和支气管活检组织 受试者将在过敏原攻击后的不同时间进行检查。单元格 每种细胞因子的来源将通过原位杂交来确定， 免疫组织化学在活检组织中的应用，并通过FACS分析和功能研究 在BAL细胞中。研究人员推测，在接触过敏原后， 嗜碱性粒细胞被迅速招募到呼吸道，是最初的主要来源 IL-4和IL-13，而T淋巴细胞招募较慢，代表 IL-5的主要来源。调查人员还假设，一种新的 已描述的细胞因子，组胺释放因子(HRF)，在 通过激活渗入的嗜碱性粒细胞和嗜酸性粒细胞而引起的哮喘。因此，他们 将评估HRF水平并确定呼吸道后HRF的细胞位置 在挑战和急性和慢性哮喘发作中。

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.