Functional analysis of the Ym2 chitinase-like lectin in allergic airways disease

Ym2几丁质酶样凝集素在过敏性气道疾病中的功能分析

• 批准号: nhmrc : 366765
• 负责人: A/Pr Marco Casarotto
• 金额: $ 18.92万
• 依托单位: Australian National University
• 依托单位国家: 澳大利亚
• 项目类别: NHMRC Project Grants
• 财政年份: 2006
• 资助国家: 澳大利亚
• 起止时间: 2006-01-01 至 2008-12-31
• 项目状态: 已结题
• 来源: https://researchdata.edu.au/functional-analysis-ym2-airways-disease/98427
• 关键词: Functional; analysis; Ym2; chitinase; like

The prevalence of asthma is widespread and nationally affects over two million Australians. Consequently, one of the Country s National Health Priorities is to improve our understanding of this condition. Analyses of the asthmatic lung reveal an airway wall that is thickened, an airway lumen that is obstructed and abnormal spasmogenicity of the airway smooth muscle: processes that collectively contribute to both acute and chronic respiratory dysfunction. Asthmatics develop an immune response that is biased toward production of allergy-related T helper 2 cytokines of which interleukin (IL)-13 is a potent mediator of disease. However, the molecular processes linking IL-13 with abnormal airway wall changes are unclear. To identify previously uncharacterised IL-13-related molecules, we used a protein profiling approach that identified a novel lectin (carbohydrate-binding protein) termed Ym2, which is secreted abundantly into the airway fluid of mice in which allergic airways disease has been induced. Preliminary studies suggest that Ym2 is an intermediary of IL-13 that is involved in respiratory dysfunction. This project aims to work out how Ym2 interacts with the molecules and cells of the respiratory tract to regulate allergic disease. Specific inhibitors of Ym2 will be developed to examine what happens to allergic responses when Ym2 can t function; transgenic mice will be developed to determine if we see features of allergy when Ym2 is over-expressed in the normal lung, and human samples will be screened to identify the human counterpart of Ym2 and whether this counterpart is secreted into the lung fluid of asthmatics. Defining the mechanism by which Ym2 regulates the pathogenesis of allergic disease will not only contribute to our basic understanding of the processes underlying asthma pathology, but also generate new information for better design of therapeutics directed against specific mediators of this debilitating and widespread disease.

哮喘的患病率很普遍，在全国范围内影响着200多万澳大利亚人。因此，我国的国家卫生优先事项之一就是提高我们对这种情况的了解。对哮喘肺的分析显示气道壁增厚，气道管腔阻塞，气道平滑肌痉挛性异常：这些过程共同导致急性和慢性呼吸功能障碍。哮喘患者产生一种免疫反应，偏向于产生过敏相关的辅助性T - 2细胞因子，其中白细胞介素(IL)-13是一种有效的疾病介质。然而，将IL-13与气道壁异常改变联系起来的分子过程尚不清楚。为了鉴定以前未表征的il -13相关分子，我们使用了一种蛋白质分析方法，鉴定了一种称为Ym2的新型凝集素（碳水化合物结合蛋白），该凝集素大量分泌到诱导过敏性气道疾病的小鼠气道液中。初步研究表明，Ym2是参与呼吸功能障碍的IL-13的中介。该项目旨在研究Ym2如何与呼吸道的分子和细胞相互作用以调节过敏性疾病。将开发特异性的Ym2抑制剂，以检查当Ym2不能发挥作用时过敏反应会发生什么；将开发转基因小鼠，以确定当Ym2在正常肺中过度表达时，我们是否看到过敏特征，并筛选人类样本，以确定Ym2的人类对应物，以及这种对应物是否分泌到哮喘患者的肺液中。确定Ym2调控变应性疾病发病机制不仅有助于我们对哮喘病理过程的基本理解，而且为更好地设计针对这种使人衰弱和广泛疾病的特定介质的治疗方法提供了新的信息。