Asthma, airway Inflammation and beta Chemokine Receptors

描述(申请人提供)：哮喘，呼吸道炎症和β-趋化因子受体。在过去的五年里，从对小鼠体内趋化因子及其受体的研究中收集到了大量的信息。在我们之前的方案中，我们假设β趋化因子及其受体对于嗜酸性粒细胞基础和变态反应运输到肺以及淋巴细胞到致敏肺是必不可少的。到目前为止，我们的数据支持这一假设，但很明显，生理学比最初估计的要复杂得多。为了完成我们对嗜酸性粒细胞和淋巴细胞向炎症小鼠肺的转运的研究，我们建议1)继续表征β-趋化因子受体在白细胞向肺重新募集中的作用2)评估CCR3诱导气道反应性反常表型的机制3)通过使用嗜酸性粒细胞系消融的小鼠系来评估嗜酸性粒细胞和CCR3在过敏反应中的作用。我们1996年开始的工作的成功完成应该会使我们更清楚地认识到趋化因子在体内的作用，并为哮喘的新抗炎策略提供潜在的线索。

DESCRIPTION (provided by applicant): Asthma, Airway Inflammation and Beta Chemokine Receptors. Over the past five years, an explosion of information has been gleaned from studies of chemokines and their receptors in the mouse. In our previous proposal, we hypothesized that beta chemokines and their receptors were essential for basal as well as allergic trafficking of eosinophils to the lung, and lymphocytes to the sensitized lung. Our data to date support this hypothesis, but it has become clear that the physiology is more complex than initially appreciated. In order to complete our studies of eosinophil and lymphocyte trafficking to the inflamed murine lung, we propose to 1) continue to characterize the role of beta chemokine receptors in leukocyte recruitment to lung 2) To evaluate the mechanism by which CCR3 elicits airways paradoxical phenotypes in airways responsiveness 3) to evaluate the role of eosinophils and CCR3 in allergic responses through the use of an eosinophil-lineage ablated mouse line. Successful completion of the work we began in 1996 should lead to a more clear appreciation of the role of chemokines in vivo, and potential leads for new anti-inflammatory strategies in asthma.