Sulfated glycans induce rapid hematopoietic progenitor cell mobilization: evidence for selectin-dependent and independent mechanisms

The adhesive mechanisms leading to the mobilization of hematopoietic progen itor cells (HPCs) from the bone marrow into the blood are poorly understood . We report on a role for selectins and fucoidan in progenitor mobilization , Baseline levels of circulating HPCs are increased in endothelial selectin -deficient (P/E-/-) mice. Similar levels are observed when E-selectin null (E-/-) mice are treated with anti-P-selectin antibody or with fucoidan (whi ch inhibits P- and L-selectin function). In particular, administration of 2 doses of fucoidan (25 mg/kg) over 6 hours produces profound mobilization o f progenitors in wild-type mice and the response is greatly enhanced in E-/ - and P/E-/- mice. Competitive reconstitution experiments reveal that fucoi dan also elicits long-term (more than 6 months) repopulating stem cells. Mo bilization assays using chimeric mice harboring L- selectin-deficient proge nitors and wildtype progenitors expressing the green fluorescence protein s uggest that L-selectin expression is not required but confers an advantage for fucoidan-induced mobilization. Sulfation is critical as desulfated fuco idan is ineffective. In addition, sulphogalactosylceramide (sulfatide) but not heparin can induce HPC mobilization. Our results indicate that administ ration of sulfated glycans, especially with concurrent inhibition of E-sele ctin function, represents a powerful novel method for rapid mobilization of long-term-repopulating stem cells. These findings may help elucidate the m echanisms of HPC trafficking during development and adult life. (Blood. 200 0;96:2460-2468) (C) 2000 by The American Society of Hematology.