[PDF][PDF] Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence

C Martin, PCE Burdon, G Bridger, JC Gutierrez-Ramos… - Immunity, 2003 - cell.com
C Martin, PCE Burdon, G Bridger, JC Gutierrez-Ramos, TJ Williams, SM Rankin
Immunity, 2003cell.com
In this study we provide evidence that the SDF-1α/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-1α, 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 …
Abstract
In this study we provide evidence that the SDF-1α/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-1α, 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-1α using a specific CXCR4 antagonist. As neutrophils age, they upregulate expression of CXCR4 and acquire the ability to migrate toward SDF-1α. We show here that these senescent CXCR4high 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.
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