The integrin αMβ2 anchors hematopoietic progenitors in the bone marrow during enforced mobilization

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 αMβ2 (macrophage antigen-1 [Mac-1]) and L-selectin resulting in αMβ2-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 αM (αM ^-/-) compared with wild-type (αM^+/+) animals and higher plasma levels of the chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) were achieved in αM^-/- mice by fucoidan treatment. However, in chimeric animals harboring αM^+/+ and αM ^-/- HPCs in the BM, αM^-/- HPCs were preferentially mobilized by fucoidan, suggesting that the enhanced mobilization is cell intrinsic and does not result from altered microenvironment. Suboptimal doses of granulocyte colony-stimulating factor (G-CSF) or cyclophosphamide (CY) also resulted in enhanced HPC mobilization in αM^-1- mice compared with αM^+/+ controls, but this difference was overcome when standard doses of G-CSF or CY were administered. Taken together, these data suggest that the integrin αMβ2 participates in the retention of HPCs in the BM.