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Blood, 15 August 2004, Vol. 104, No. 4, pp. 993-1001.
Prepublished online as a Blood First Edition Paper on April 20, 2004; DOI 10.1182/blood-2003-10-3702.
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Submitted October 29, 2003
Accepted April 5, 2004
The integrin M 2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization
Andres Hidalgo, Anna J Peired, Linnea A Weiss, Yoshio Katayama, and Paul S Frenette*
Medicine and Immunobiology Center, Mount Sinai School of Medicine, New York, NY, USA
* Corresponding author; email: paul.frenette{at}mssm.edu.
The sulfated polysaccharide fucoidan can rapidly mobilize hematopoietic progenitor cells (HPCs) and long-term repopulating stem cells from the bone marrow (BM) to the circulation. While searching for mechanisms involved in this phenomenon, we found that BM myeloid cells bound to fucoidan through the integrin M 2 (Mac-1) and L-selectin, resulting in M 2-independent release of neutrophil elastase, but inhibition of elastase activity did not impair fucoidan-induced mobilization. Mobilization of HPCs by fucoidan was enhanced in animals deficient in M ( M-/-) compared to wild-type ( M+/+) animals and higher plasma levels of the chemokine CXCL12/SDF-1 were achieved in M-/- mice by fucoidan treatment. However, in chimeric animals harboring M+/+ and M-/- HPCs in the BM, M-/- HPCs were preferentially mobilized by fucoidan, suggesting that the enhanced mobilization is cell-intrinsic and does not result not from altered microenvironment. Suboptimal doses of G-CSF or cyclophosphamide (CY) also resulted in enhanced HPC mobilization in M-/- mice compared to M+/+ controls, but this difference was overcome when standard doses of G-CSF or CY were administered. Taken together, these data suggest that the integrin M 2 participates in the retention of HPCs in the BM.

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