CXCR is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions

摘要

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 CXCL, through its major receptor CXCR, plays a key role in maintaining neutrophil homeosta-sis. Herein, we generated mice with a my-eloid lineage-restricted deletion of CXCR to define the mechanisms by which CXCR signals regulate this process. We show that CXCR negatively regulates neutrophil release from the bone marrow in a cell-autonomous fashion. However, CXCR is dispensable for neutrophil clearance from the circulation. Neutrophil mobilization responses to granulocyte colony-stimulating factor (G-CSF), CXCL, or Listeria monocy-togenes infection are absent or impaired, suggesting that disruption of CXCR signaling may be a common step mediating neutrophil release. Collectively, these data suggest that CXCR signaling maintains neutrophil homeostasis in the blood under both basal and stress granulopoiesis conditions primarily by regulating neutrophil release from the bone marrow.