Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence
Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence
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DOI：
10.1016/s1074-7613(03)00263-2
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发表时间：
2003-10-01
期刊：
影响因子：
32.4
通讯作者：
Rankin, SM
中科院分区：
文献类型：
--
作者：
Martin, C;Burdon, PCE;Rankin, SM
在这项研究中，我们提供的证据表明，SDF-1α/CXCR4趋化因子轴参与中性粒细胞在骨髓内的保留和衰老中性粒细胞归巢回骨髓。我们发现，新鲜分离的人和鼠中性粒细胞对 CXCR2 趋化因子的功能反应被 SDF-1α 通过 CXCR4 作用而显着减弱。因此，通过使用特定的 CXCR4 拮抗剂阻断内源性 SDF-1α 的作用，CXCR2 趋化因子 KC 在体内动员中性粒细胞的能力得到显着增强。随着中性粒细胞年龄的增长，它们会上调 CXCR4 的表达并获得向 SDF-1α 迁移的能力。我们在这里表明，这些衰老的CXCR4（高）中性粒细胞在体内以CXCR4依赖性方式优先归巢于骨髓，这表明先前未定义的从循环中清除衰老中性粒细胞的机制。
In this study we provide evidence that the SDF-1alpha/ CXCR4 chemokine axis is involved in both the retention of neutrophils within the bone marrow and the homing of senescent neutrophils back to the bone marrow. We show that the functional responses of freshly isolated human and murine neutrophils to CXCR2 chemokines are significantly attenuated by SDF-1alpha, acting via CXCR4. As a consequence, the mobilization of neutrophils from the bone marrow in vivo by the CXCR2-chemokine, KC, was dramatically enhanced by blocking the effects of endogenous SDF-1alpha using a specific CXCR4 antagonist. As neutrophils age, they upregulate expression of CXCR4 and acquire the ability to migrate toward SDF-1alpha. We show here that these senescent CXCR4(high) neutrophils preferentially home to the bone marrow in vivo in a CXCR4-dependent manner, suggesting a previously undefined mechanism for the clearance of senescent neutrophils from the circulation.