CCR3 IN AIRWAY HYPERRESPONSIVENES & EOSINOPHIL MIGRATION

CCR3 在气道高反应性中的作用

• 批准号: 6212293
• 负责人: ALISON A HUMBLES
• 金额: $ 3.75万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-03 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6212293
• 关键词: T lymphocyte; allergens; cell migration; chemokine; cytokine receptors; eosinophil; inflammation; laboratory mouse; methacholine; respiratory disorder

The beta chemokine receptor CCR3 is highly expressed on eosinophils, basophils and to a lesser extent on TH2 lymphocytes. Noteworthy, these cell types are all critical for the development of an inflammatory allergic response. Concomittantly, the expression of the ligands for this receptor, eotaxin, eotaxin-2, MCP-3, 4 and RANTES, have all been associated with disease states where eosinophils are prevalent, e.g. allergic asthma, helminthic parasitic infection and ulcerative colitis. To investigate that eosinophils are required for eosinophil trafficking in normal and inflammatory disease states, we have generated mice deficient in this receptor. We hypothesize that activated eosinophil trafficking to sensitized lungs is largely CCR3 dependent but believe that other mediators also play a role, we anticipate that the complement receptor C3aR is one such mediator. Preliminary data provide an unexpected role for CCR3 in regulating intinsic airway tone, study of the mechanisms of this receptor's role in airway hyperreponsiveness may provide insight into disease initiation and opportunity for development and evaluation of therapeutic interventions.

β趋化因子受体CCR 3在嗜酸性粒细胞、嗜碱性粒细胞上高度表达，在TH 2淋巴细胞上表达程度较低。值得注意的是，这些细胞类型对于炎症过敏反应的发展都是至关重要的。 同时，该受体的配体，嗜酸性粒细胞活化趋化因子、嗜酸性粒细胞活化趋化因子-2、MCP-3、4和RANTES的表达都与嗜酸性粒细胞普遍存在的疾病状态有关，例如过敏性哮喘、蠕虫寄生虫感染和溃疡性结肠炎。 为了研究嗜酸性粒细胞在正常和炎性疾病状态下的嗜酸性粒细胞运输所需的嗜酸性粒细胞，我们产生了这种受体缺陷的小鼠。 我们假设活化的嗜酸性粒细胞运输到致敏的肺在很大程度上是CCR 3依赖的，但相信其他介质也起作用，我们预计补体受体C3 aR是这样一种介质。 初步的数据提供了一个意想不到的作用，CCR 3在调节intinsic气道紧张，研究这种受体的作用在气道高反应性的机制可能会提供洞察疾病的启动和机会的发展和评估的治疗干预措施。