MAST CELL SIGNALING IN ASTHMA AND ALLERGIC INFLAMMATION

腺苷在变态反应性疾病的发病机制中起重要作用 哮喘。尽管多个腺苷受体亚型 介入性过敏性哮喘是争议的主题。这个 首席研究员现在建议利用基因敲除小鼠 腺苷A2a、A2b和A3受体表达均不足 过敏性肺病相关受体亚型的确定 发炎。激活的信号转导通路 正常和腺苷来源的肥大细胞上的腺苷受体 受体基因敲除小鼠也将接受测试。假设 呼吸道炎症的存在可诱导肺肥大细胞 对腺苷的高反应性，在体外将表现为 促进肥大细胞和体内组胺的释放 腺苷诱导的支气管痉挛。这些实验也将是 腺苷受体在哮喘小鼠模型中的应用 有缺陷的小鼠。肥大细胞在这些反应中的作用也将 通过在肥大细胞缺陷的情况下进行这些实验进行测试 老鼠。生物化学和分子生物学技术将成为 用来确定PI3激酶是否调节肥大细胞 脱颗粒，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.