MAST CELL SIGNALING IN ASTHMA AND ALLERGIC INFLAMMATION

腺苷在过敏性鼻炎的发病机制中起重要作用 哮喘 虽然多种腺苷受体亚型， 介导过敏性哮喘是一个有争议的话题。 的 首席研究员现在提议利用基因敲除小鼠 腺苷A2a、A2b和A3受体表达各有缺陷 以确定参与过敏性肺疾病的受体亚型， 炎症 激活的信号转导通路 正常肥大细胞和腺苷受体 还将测试受体敲除小鼠。 的假设 气道炎症的存在诱导肺肥大细胞 对腺苷的高反应性，将在体外表征为 增加肥大细胞和体内组胺释放， 腺苷引起的支气管痉挛 这些实验也将 在小鼠哮喘模型中进行腺苷受体 缺陷小鼠 肥大细胞在这些反应中的作用也将 通过在肥大细胞缺乏的小鼠中进行这些实验来测试 小鼠 生物化学和分子生物学技术将是 用于确定PI3激酶是否调节肥大细胞 脱粒，但不释放细胞因子或产生白三烯。

Adenosine plays an important role in the pathogenesis of allergic asthma. Although multiple adenosine receptor subtype that mediates allergic asthma is the subject of controversy. The principal investigator now proposes to utilize knockoutmice deficient in each of adenosine A2a, A2b and A3 receptor expression to determine the receptor subtype involved in allergic pulmonary inflammation. The signal transduction pathway activated by adenosine receptor in mast cells derived from normal and adenosine receptor knockout mice will also be tested. The hypothesis that presence of airway inflammation induces a pulmonary mast cell hyperesponsiveness to adenosine, will be characterized in vitro by increased histamine release from mast cells an in vivo by adenosine-induced bronchospasm. These experiments will also be performed in mouse model of asthma in adenosine receptor deficient mice. The role of mast cells in these responses will also be tested by performing these experiments in mast cell deficient mice. Biochemical and molecular biology techniques will be utilized to determine whether PI3 kinase regulates mast cell degranulation but not cytokine release or leukotriene production.