Hemolysis Requires Attenuation of SDF-1-CXCR4 Retention Signaling in Bone Marrow

Copyright © 2013 Kasia Mierzejewska et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, onemight assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would inducemobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ).We observed that doubling the S1P level in PB from damaged erythrocytes induced only amarginally increased level of mobilization. However, if mice were exposed to PHZ together with the CXCR4 blocking agent, AMD3100, a robust synergistic increase in the number of mobilized HSPCs occurred. We conclude that hemolysis, even if it significantly elevates the S1P level in PB, also requires attenuation of the CXCR4-SDF-1 axis-mediated retention in BM niches for HSPCmobilization to occur. Our data also further confirm that S1P is a major chemottractant present in plasma and chemoattracts HSPCs into PB under steady-state conditions. However, to egress from BM, HSPCs first hav