Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells

A. Dar, A. Schajnovitz, K. Lapid, A. Kalinkovich, T. Itkin, A. Ludin, W. M. Kao, M. Battista, M. Tesio, O. Kollet, N. N. Cohen, R. Margalit, E. C. Buss, F. Baleux, S. Oishi, N. Fujii, A. Larochelle, C. E. Dunbar, H. E. Broxmeyer, Paul S. FrenetteT. Lapidot

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4 + human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.

Original languageEnglish (US)
Pages (from-to)1286-1296
Number of pages11
JournalLeukemia
Volume25
Issue number8
DOIs
StatePublished - Aug 2011
Externally publishedYes

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Chemokine CXCL12
Mesenchymal Stromal Cells
Catecholamines
Stem Cells
Hematopoietic Stem Cells
Chemokines
Leukocytes
JM 3100
Adrenergic Antagonists
Neutralizing Antibodies
Osteoblasts
Bone Marrow Cells
Primates
Norepinephrine
Endothelial Cells
Bone and Bones
Injections

Keywords

  • AMD3100
  • catecholamines
  • hematopoietic progenitor cells
  • rapid mobilization
  • SDF-1/CXCR4
  • uPA

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. / Dar, A.; Schajnovitz, A.; Lapid, K.; Kalinkovich, A.; Itkin, T.; Ludin, A.; Kao, W. M.; Battista, M.; Tesio, M.; Kollet, O.; Cohen, N. N.; Margalit, R.; Buss, E. C.; Baleux, F.; Oishi, S.; Fujii, N.; Larochelle, A.; Dunbar, C. E.; Broxmeyer, H. E.; Frenette, Paul S.; Lapidot, T.

In: Leukemia, Vol. 25, No. 8, 08.2011, p. 1286-1296.

Research output: Contribution to journalArticle

Dar, A, Schajnovitz, A, Lapid, K, Kalinkovich, A, Itkin, T, Ludin, A, Kao, WM, Battista, M, Tesio, M, Kollet, O, Cohen, NN, Margalit, R, Buss, EC, Baleux, F, Oishi, S, Fujii, N, Larochelle, A, Dunbar, CE, Broxmeyer, HE, Frenette, PS & Lapidot, T 2011, 'Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells', Leukemia, vol. 25, no. 8, pp. 1286-1296. https://doi.org/10.1038/leu.2011.62
Dar, A. ; Schajnovitz, A. ; Lapid, K. ; Kalinkovich, A. ; Itkin, T. ; Ludin, A. ; Kao, W. M. ; Battista, M. ; Tesio, M. ; Kollet, O. ; Cohen, N. N. ; Margalit, R. ; Buss, E. C. ; Baleux, F. ; Oishi, S. ; Fujii, N. ; Larochelle, A. ; Dunbar, C. E. ; Broxmeyer, H. E. ; Frenette, Paul S. ; Lapidot, T. / Rapid mobilization of hematopoietic progenitors by AMD3100 and catecholamines is mediated by CXCR4-dependent SDF-1 release from bone marrow stromal cells. In: Leukemia. 2011 ; Vol. 25, No. 8. pp. 1286-1296.
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abstract = "Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4 + human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.",
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AU - Dar, A.

AU - Schajnovitz, A.

AU - Lapid, K.

AU - Kalinkovich, A.

AU - Itkin, T.

AU - Ludin, A.

AU - Kao, W. M.

AU - Battista, M.

AU - Tesio, M.

AU - Kollet, O.

AU - Cohen, N. N.

AU - Margalit, R.

AU - Buss, E. C.

AU - Baleux, F.

AU - Oishi, S.

AU - Fujii, N.

AU - Larochelle, A.

AU - Dunbar, C. E.

AU - Broxmeyer, H. E.

AU - Frenette, Paul S.

AU - Lapidot, T.

PY - 2011/8

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N2 - Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4 + human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.

AB - Steady-state egress of hematopoietic progenitor cells can be rapidly amplified by mobilizing agents such as AMD3100, the mechanism, however, is poorly understood. We report that AMD3100 increased the homeostatic release of the chemokine stromal cell derived factor-1 (SDF-1) to the circulation in mice and non-human primates. Neutralizing antibodies against CXCR4 or SDF-1 inhibited both steady state and AMD3100-induced SDF-1 release and reduced egress of murine progenitor cells over mature leukocytes. Intra-bone injection of biotinylated SDF-1 also enhanced release of this chemokine and murine progenitor cell mobilization. AMD3100 directly induced SDF-1 release from CXCR4 + human bone marrow osteoblasts and endothelial cells and activated uPA in a CXCR4/JNK-dependent manner. Additionally, ROS inhibition reduced AMD3100-induced SDF-1 release, activation of circulating uPA and mobilization of progenitor cells. Norepinephrine treatment, mimicking acute stress, rapidly increased SDF-1 release and progenitor cell mobilization, whereas β2-adrenergic antagonist inhibited both steady state and AMD3100-induced SDF-1 release and progenitor cell mobilization in mice. In conclusion, this study reveals that SDF-1 release from bone marrow stromal cells to the circulation emerges as a pivotal mechanism essential for steady-state egress and rapid mobilization of hematopoietic progenitor cells, but not mature leukocytes.

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KW - catecholamines

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