CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses.
CXCR2 deficient mice display macrophage-dependent exaggerated acute inflammatory responses.
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DOI：
10.1038/srep42681
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发表时间：
2017-02-16
影响因子：
4.6
通讯作者：
Graham GJ
中科院分区：
文献类型：
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作者：
Dyer DP;Pallas K;Medina-Ruiz L;Schuette F;Wilson GJ;Graham GJ
CXCR2 是中性粒细胞募集至发炎和受损部位的重要调节因子，在炎症病理和癌症中发挥着重要作用。因此，它被强调为重要的治疗靶点。然而，由于我们对其精确的体内作用模式相对缺乏了解，CXCR2 治疗靶向的成功受到威胁。在这里，我们证明CXCR2缺陷小鼠对皮肤和腹膜炎症刺激表现出违反直觉的短暂夸大炎症反应。在这两种情况下，这都与炎症反应消退相关的细胞因子表达减少以及炎症部位巨噬细胞积聚增加有关。使用中性粒细胞耗竭策略的分析表明，这是非中性粒细胞 CXCR2 阳性白细胞群招募受损的结果。我们认为这些细胞可能是骨髓来源的抑制细胞。因此，我们的数据揭示了 CXCR2 在炎症反应协调中的新颖且先前未预料到的作用。
CXCR2 is an essential regulator of neutrophil recruitment to inflamed and damaged sites and plays prominent roles in inflammatory pathologies and cancer. It has therefore been highlighted as an important therapeutic target. However the success of the therapeutic targeting of CXCR2 is threatened by our relative lack of knowledge of its precise in vivo mode of action. Here we demonstrate that CXCR2-deficient mice display a counterintuitive transient exaggerated inflammatory response to cutaneous and peritoneal inflammatory stimuli. In both situations, this is associated with reduced expression of cytokines associated with the resolution of the inflammatory response and an increase in macrophage accumulation at inflamed sites. Analysis using neutrophil depletion strategies indicates that this is a consequence of impaired recruitment of a non-neutrophilic CXCR2 positive leukocyte population. We suggest that these cells may be myeloid derived suppressor cells. Our data therefore reveal novel and previously unanticipated roles for CXCR2 in the orchestration of the inflammatory response.