CCR3 IN AIRWAY HYPERRESPONSIVENES & EOSINOPHIL MIGRATION

趋化因子受体CCR3在嗜酸性粒细胞和嗜碱性粒细胞上高度表达，在TH2淋巴细胞上表达较少。值得注意的是，这些细胞类型都对炎症过敏反应的发展至关重要。同时，这种受体的配体eotaxin、eotaxin-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、寄生虫感染和溃疡性结肠炎。为了研究在正常和炎症疾病状态下嗜酸性粒细胞运输是否需要嗜酸性粒细胞，我们产生了这种受体缺乏的小鼠。我们假设活化的嗜酸性粒细胞运输到致敏的肺部在很大程度上依赖于CCR3，但相信其他介质也起作用，我们预计补体受体C3aR是这样的介质之一。初步数据提供了CCR3在调节气道固有张力中的意想不到的作用，研究该受体在气道高反应性中的作用机制可能为疾病的发生提供见解，并为治疗干预的开发和评估提供机会。

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.