The integrin alphaMbeta2 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 alphaMbeta2 (macrophage antigen-1 [Mac-1]) and L-selectin resulting in alphaMbeta2-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 alphaM (alphaM-/-) compared with wild-type (alphaM+/+) animals and higher plasma levels of the chemokine CXCL12/stromal cell-derived factor-1 (SDF-1) were achieved in alphaM-/- mice by fucoidan treatment. However, in chimeric animals harboring alphaM+/+ and alphaM-/- HPCs in the BM, alphaM-/- 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 alphaM-/- mice compared with alphaM+/+ controls, but this difference was overcome when standard doses of G-CSF or CY were administered. Taken together, these data suggest that the integrin alphaMbeta2 participates in the retention of HPCs in the BM.
Hidalgo
Andrés
A
Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1079, New York, NY 10029, USA.
Peired
Anna J
AJ
Weiss
Linnea A
LA
Katayama
Yoshio
Y
Frenette
Paul S
PS
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood; D003520:Cyclophosphamide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D019272:Leukocyte Elastase / Q000378:metabolism; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D011134:Polysaccharides / Q000378:metabolism / Q000494:pharmacology
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016177:Macrophage-1 Antigen; D011134:Polysaccharides; D019041:L-Selectin; D016179:Granulocyte Colony-Stimulating Factor; D003520:Cyclophosphamide; C007789:fucoidan; D019272:Leukocyte Elastase