AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway Hyperreactivity
AMD3100, a CxCR4 antagonist, attenuates allergic lung inflammation and airway Hyperreactivity
复制标题
DOI：
10.1016/s0002-9440(10)62562-x
复制
发表时间：
2002-04-01
影响因子：
6
通讯作者：
Bridger, GJ
中科院分区：
文献类型：
--
作者：
Lukacs, NW;Berlin, A;Bridger, GJ
特异性趋化因子受体在过敏性哮喘反应中的作用尚不明确。许多受体在Th2细胞上优先表达，包括CCR4、CCR8和CXCR4。在本研究中，我们研究了CXCR4在蟑螂变应原诱导的炎症和哮喘小鼠模型中的气道高反应性发展中的作用。使用CXCR4的特异性抑制剂AMD3100，我们的结果表明，阻断该受体在下调过敏原诱导的反应的炎症和病理生理方面具有显著效果。用AMD3100治疗过敏性小鼠可显著降低气道高反应性、支气管周围嗜酸性粒细胞增多和整体炎症反应。此外，在AMD3100治疗的动物中观察到的细胞因子谱发生了变化。具体地说，治疗后过敏小鼠肺内白介素4和白介素5水平显著降低，白介素12和干扰素-伽马水平显著升高。此外，CCL22(MDC)和CCL17(TARC)的局部趋化因子的产生也发生了显著变化，这两种趋化因子以前被证明在Th2型变应原反应中起重要作用。总体而言，使用AMD3100特异性阻断CXCR4可以减少与哮喘型炎症相关的一些病理参数。
The role of specific chemokine receptors during allergic asthmatic responses has been relatively undefined. A number of receptors are preferentially expressed on Th2 cells, including CCR4, CCR8, and CxCR4. in the present study, we have examined the role of CxCR4 in the development of cockroach allergen-induced inflammation and airway hyperreactivity in a mouse model of asthma. Using a specific inhibitor of CxCR4, AMD3100, our results indicate that blocking this receptor has a significant effect in down-regulating the inflammation and pathophysiology of the allergen-induced response. Treatment of allergic mice with AMD3100 significantly reduced airway hyperreactivity, peribronchial eosinophilia, and the overall inflammatory responses. in addition, there was a shift in the cytokine profile that was observed in the AMD3100-treated animals. Specifically, there was a significant reduction in interleukin-4 and interleukin-5 levels and a significant increase in interleukin-12 and interferon-gamma levels within the lungs of treated allergic mice. Furthermore, there was a significant alteration in the local chemokine production of CCL22 (MDC) and CCL17 (TARC), two chemokines previously shown to be important in Th2-type allergen responses. overall, specifically blocking CxCR4 using AMD3100 reduced a number of pathological parameters related to asthmatic-type inflammation.