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

被引:36
作者
Hidalgo, A
Peired, AJ
Weiss, LA
Katayama, Y
Frenette, PS
机构
[1] CUNY Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA
[2] CUNY Mt Sinai Sch Med, Immunobiol Ctr, New York, NY 10029 USA
关键词
D O I
10.1182/blood-2003-10-3702
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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. (C) 2004 by The American Society of Hematology.
引用
收藏
页码:993 / 1001
页数:9
相关论文
共 52 条
[31]   THE PURIFICATION AND CHARACTERIZATION OF FETAL LIVER HEMATOPOIETIC STEM-CELLS [J].
MORRISON, SJ ;
HEMMATI, HD ;
WANDYCZ, AM ;
WEISSMAN, IL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (22) :10302-10306
[32]   Mechanisms of stem-/progenitor-cell mobilization: The anti-VLA-4 paradigm [J].
Papayannopoulou, T .
SEMINARS IN HEMATOLOGY, 2000, 37 (01) :11-18
[33]   THE VLA4/VCAM-1 ADHESION PATHWAY DEFINES CONTRASTING MECHANISMS OF LODGEMENT OF TRANSPLANTED MURINE HEMATOPOIETIC PROGENITORS BETWEEN BONE-MARROW AND SPLEEN [J].
PAPAYANNOPOULOU, T ;
CRADDOCK, C ;
NAKAMOTO, B ;
PRIESTLEY, GV ;
WOLF, NS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (21) :9647-9651
[34]   Heparin inhibits ligand binding to the leukocyte integrin Mac-1 (CD11b/CD18) [J].
Peter, K ;
Schwarz, M ;
Conradt, C ;
Nordt, T ;
Moser, M ;
Kübler, W ;
Bode, C .
CIRCULATION, 1999, 100 (14) :1533-1539
[35]   G-CSF induces stem cell mobilization by decreasing bone marrow SDF-1 and up-regulating CXCR4 [J].
Petit, I ;
Szyper-Kravitz, M ;
Nagler, A ;
Lahav, M ;
Peled, A ;
Habler, L ;
Ponomaryov, T ;
Taichman, RS ;
Arenzana-Seisdedos, F ;
Fujii, N ;
Sandbank, J ;
Zipori, D ;
Lapidot, T .
NATURE IMMUNOLOGY, 2002, 3 (07) :687-694
[36]   Defective LPS signaling in C3H/HeJ and C57BL/10ScCr mice:: Mutations in Tlr4 gene [J].
Poltorak, A ;
He, XL ;
Smirnova, I ;
Liu, MY ;
Van Huffel, C ;
Du, X ;
Birdwell, D ;
Alejos, E ;
Silva, M ;
Galanos, C ;
Freudenberg, M ;
Ricciardi-Castagnoli, P ;
Layton, B ;
Beutler, B .
SCIENCE, 1998, 282 (5396) :2085-2088
[37]   Neutrophils are indispensable for hematopoietic stem cell mobilization induced by interleukin-8 in mice [J].
Pruijt, JFM ;
Verzaal, P ;
van Os, R ;
de Kruijf, EJFM ;
van Schie, MLJ ;
Mantovani, A ;
Vecchi, A ;
Lindley, IJD ;
Willemze, R ;
Starckx, S ;
Opdenakker, G ;
Fibbe, WE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (09) :6228-6233
[38]   Phenotypic and functional changes induced at the clonal level in hematopoietic stem cells after 5-fluorouracil treatment [J].
Randall, TD ;
Weissman, IL .
BLOOD, 1997, 89 (10) :3596-3606
[39]   Multiple, targeted deficiencies in selectins reveal a predominant role for P-selectin in leukocyte recruitment [J].
Robinson, SD ;
Frenette, PS ;
Rayburn, H ;
Cummiskey, M ;
Ullman-Culleré, M ;
Wagner, DD ;
Hynes, RO .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (20) :11452-11457
[40]   Role of the lectin domain of Mac-1/CR3 (CD11b/CD18) in regulating intercellular adhesion [J].
Ross, GD .
IMMUNOLOGIC RESEARCH, 2002, 25 (03) :219-227