Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence.
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.
Martin
Coralie
C
Leukocyte Biology Section, Division of Biomedical Sciences, Faculty of Medicine, Imperial College School of Science, Technology and Medicine, Sir Alexander Fleming Building, Exhibition Road, South Kensington, London SW7 2AZ, UK.
Burdon
Peter C E
PC
Bridger
Gary
G
Gutierrez-Ramos
Jose Carlos
JC
Williams
Timothy J
TJ
Rankin
Sara M
SM
D000818:Animals; D001853:Bone Marrow / Q000378:metabolism*; D054377:Chemokine CXCL12; D018925:Chemokines / Q000378:metabolism*; D019743:Chemokines, CXC / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000378:metabolism*; D023063:Receptors, Interleukin-8B / Q000378:metabolism*
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D018925:Chemokines; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D019718:Receptors, CXCR4; D023063:Receptors, Interleukin-8B