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Blood, 1 October 2000, Vol. 96, No. 7, pp. 2460-2468
HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY
Sulfated glycans induce rapid hematopoietic progenitor cell
mobilization: evidence for selectin-dependent and independent
mechanisms
Paul S. Frenette and
Linnea Weiss
From the Mount Sinai School of Medicine, Department of
Medicine, New York, NY.
The adhesive mechanisms leading to the mobilization of
hematopoietic progenitor 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 (which inhibits
P- and L-selectin function). In particular, administration of 2 doses
of fucoidan (25 mg/kg) over 6 hours produces profound mobilization of
progenitors in wild-type mice and the response is greatly enhanced in
E / and P/E / mice. Competitive reconstitution experiments reveal
that fucoidan also elicits long-term (more than 6 months) repopulating
stem cells. Mobilization assays using chimeric mice harboring
L-selectin-deficient progenitors and wild-type progenitors expressing
the green fluorescence protein suggest that L-selectin expression is
not required but confers an advantage for fucoidan-induced
mobilization. Sulfation is critical as desulfated fucoidan is
ineffective. In addition, sulphogalactosylceramide (sulfatide) but not
heparin can induce HPC mobilization. Our results indicate that
administration of sulfated glycans, especially with concurrent
inhibition of E-selectin function, represents a powerful novel method
for rapid mobilization of long-term-repopulating stem cells. These
findings may help elucidate the mechanisms of HPC trafficking during
development and adult life.

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