Figure 3.

Neutrophil mobilisation by CXCR4 antagonists. Two CXCR4 antagonists AMD3100 and KRH3955, both stimulate neutrophil mobilisation into the blood, but by distinct mechanisms of action in vivo. AMD3100 interacts with the transmembrane domain of CXCR4 and stimulates the translocation of CXCL12 from the bone marrow stroma across the sinusoidal endothelium, increasing CXCL12 levels in the blood with a concomitant reduction in CXCL12 levels in the bone marrow. Neutrophils migrate in response to increased levels of CXCL12 in the blood. In contrast KRH3955 binds to the extracellular domain of CXCR4 and blocks binding of CXCL12 to the receptor, thereby directly disrupting the CXCL12/CXCR2 neutrophil retention axis in the bone marrow