CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions
CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions
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DOI：
10.1182/blood-2008-09-177287
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发表时间：
2009-05-07
期刊：
影响因子：
20.3
通讯作者：
Link, Daniel C.
中科院分区：
文献类型：
--
作者：
Eash, Kyle J.;Means, Jacquelyn M.;Link, Daniel C.
血液中中性粒细胞的数量受到严格的调节，以确保对微生物病原体的充分保护，同时最大限度地减少对宿主组织的损害。血液中的中性粒细胞稳态通过中性粒细胞产生、从骨髓释放和从循环中清除的平衡来实现。越来越多的证据表明，CXCL 12通过其主要受体CXCR 4的信号传导在维持中性粒细胞稳态中起关键作用。在此，我们产生了骨髓谱系限制性CXCR 4缺失的小鼠，以确定CXCR 4信号调节这一过程的机制。我们发现，CXCR 4负调控中性粒细胞从骨髓中释放的细胞凋亡的方式。然而，CXCR 4对于从循环中清除中性粒细胞是不利的。对粒细胞集落刺激因子（G-CSF）、CXCL 2或单核细胞增生李斯特菌感染的中性粒细胞动员反应不存在或受损，表明CXCR 4信号传导的破坏可能是介导中性粒细胞释放的共同步骤。总的来说，这些数据表明，CXCR 4信号传导主要通过调节中性粒细胞从骨髓释放来维持在基础和应激粒细胞生成条件下血液中的中性粒细胞稳态。（血。2009;113：4711-4719）
The number of neutrophils in the blood is tightly regulated to ensure adequate protection against microbial pathogens while minimizing damage to host tissue. Neutrophil homeostasis in the blood is achieved through a balance of neutrophil production, release from the bone marrow, and clearance from the circulation. Accumulating evidence suggests that signaling by CXCL12, through its major receptor CXCR4, plays a key role in maintaining neutrophil homeostasis. Herein, we generated mice with a myeloid lineage-restricted deletion of CXCR4 to define the mechanisms by which CXCR4 signals regulate this process. We show that CXCR4 negatively regulates neutrophil release from the bone marrow in a cellautonomous fashion. However, CXCR4 is dispensable for neutrophil clearance from the circulation. Neutrophil mobilization responses to granulocyte colony-stimulating factor (G-CSF), CXCL2, or Listeria monocy-togenes infection are absent or impaired, suggesting that disruption of CXCR4 signaling may be a common step mediating neutrophil release. Collectively, these data suggest that CXCR4 signaling maintains neutrophil homeostasis in the blood under both basal and stress granulopoiesis conditions primarily by regulating neutrophil release from the bone marrow. (Blood. 2009;113:4711-4719)