Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines

Younghee Lee, Akihiko Gotoh, Hyung Joo Kwon, Minute You, Lisa Kohli, Charlie Mantel, Scott Cooper, Giao Hangoc, Keisuke Miyazawa, Kazuma Ohyashiki, Hal E. Broxmeyer

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Abstract

Stromal cell-derived factor 1 (SDF-1/ CXCL12) is a multifunctional cytokine. We previously reported that myelopoiesis was enhanced in SDF-1α transgenic mice, probably due in part to SDF-1α enhancement of myeloid progenitor cell (MPC) survival. To understand signaling pathways involved in this activity, we studied the effects on factor-dependent cell line MO7e cells incubated with SDF-1α alone or in combination with other cytokines. SDF-1α induced transient activation of extracellular stress-regulated kinase (ERK1/2), ribosomal S6 kinase (p9ORSK) and Akt, molecules implicated in cell survival. Moreover, ERK1/2, p90RSK, and Akt were synergistically activated by SDF-1α in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor (SLF), or thrombopoietin (TPO). Similar effects were seen after pretreatment of MO7e cells with SDF-1α followed by stimulation with the other cytokines, suggesting a priming effect of SDF-1α. Nuclear factor-ΚB (NF-ΚB) did not appear to be involved in SDF-1α actions, alone or in combination with other cytokines. These intracellular effects were consistent with enhanced myeloid progenitor cell survival by SDF-1α after delayed addition of growth factors. SDF-1α alone supported survival of highly purified human cord blood CD34 +++ cells, less purified human cord blood, and MO7e cells; this effect was synergistically enhanced when SDF-1α was combined with low amounts of other survival-promoting cytokines (GM-CSF, SLF, TPO, and FL). SDF-1 may contribute to maintenance of MPCs in bone marrow by enhancing cell survival alone and in combination with other cytokines.

Original languageEnglish (US)
Pages (from-to)4307-4317
Number of pages11
JournalBlood
Volume99
Issue number12
DOIs
StatePublished - Jun 15 2002

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Hematopoietic Stem Cells
Cell Survival
Cells
Cytokines
Myeloid Progenitor Cells
Thrombopoietin
Stem Cell Factor
Granulocyte-Macrophage Colony-Stimulating Factor
Fetal Blood
Blood Cells
Blood
Myelopoiesis
Chemokine CXCL12
Mitogen-Activated Protein Kinase 3
Survival
Bone Marrow Cells
Transgenic Mice
Intercellular Signaling Peptides and Proteins
Bone
Chemical activation

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines. / Lee, Younghee; Gotoh, Akihiko; Kwon, Hyung Joo; You, Minute; Kohli, Lisa; Mantel, Charlie; Cooper, Scott; Hangoc, Giao; Miyazawa, Keisuke; Ohyashiki, Kazuma; Broxmeyer, Hal E.

In: Blood, Vol. 99, No. 12, 15.06.2002, p. 4307-4317.

Research output: Contribution to journalArticle

Lee, Y, Gotoh, A, Kwon, HJ, You, M, Kohli, L, Mantel, C, Cooper, S, Hangoc, G, Miyazawa, K, Ohyashiki, K & Broxmeyer, HE 2002, 'Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines', Blood, vol. 99, no. 12, pp. 4307-4317. https://doi.org/10.1182/blood.V99.12.4307
Lee, Younghee ; Gotoh, Akihiko ; Kwon, Hyung Joo ; You, Minute ; Kohli, Lisa ; Mantel, Charlie ; Cooper, Scott ; Hangoc, Giao ; Miyazawa, Keisuke ; Ohyashiki, Kazuma ; Broxmeyer, Hal E. / Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines. In: Blood. 2002 ; Vol. 99, No. 12. pp. 4307-4317.
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abstract = "Stromal cell-derived factor 1 (SDF-1/ CXCL12) is a multifunctional cytokine. We previously reported that myelopoiesis was enhanced in SDF-1α transgenic mice, probably due in part to SDF-1α enhancement of myeloid progenitor cell (MPC) survival. To understand signaling pathways involved in this activity, we studied the effects on factor-dependent cell line MO7e cells incubated with SDF-1α alone or in combination with other cytokines. SDF-1α induced transient activation of extracellular stress-regulated kinase (ERK1/2), ribosomal S6 kinase (p9ORSK) and Akt, molecules implicated in cell survival. Moreover, ERK1/2, p90RSK, and Akt were synergistically activated by SDF-1α in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor (SLF), or thrombopoietin (TPO). Similar effects were seen after pretreatment of MO7e cells with SDF-1α followed by stimulation with the other cytokines, suggesting a priming effect of SDF-1α. Nuclear factor-ΚB (NF-ΚB) did not appear to be involved in SDF-1α actions, alone or in combination with other cytokines. These intracellular effects were consistent with enhanced myeloid progenitor cell survival by SDF-1α after delayed addition of growth factors. SDF-1α alone supported survival of highly purified human cord blood CD34 +++ cells, less purified human cord blood, and MO7e cells; this effect was synergistically enhanced when SDF-1α was combined with low amounts of other survival-promoting cytokines (GM-CSF, SLF, TPO, and FL). SDF-1 may contribute to maintenance of MPCs in bone marrow by enhancing cell survival alone and in combination with other cytokines.",
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AU - Lee, Younghee

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AU - Kwon, Hyung Joo

AU - You, Minute

AU - Kohli, Lisa

AU - Mantel, Charlie

AU - Cooper, Scott

AU - Hangoc, Giao

AU - Miyazawa, Keisuke

AU - Ohyashiki, Kazuma

AU - Broxmeyer, Hal E.

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N2 - Stromal cell-derived factor 1 (SDF-1/ CXCL12) is a multifunctional cytokine. We previously reported that myelopoiesis was enhanced in SDF-1α transgenic mice, probably due in part to SDF-1α enhancement of myeloid progenitor cell (MPC) survival. To understand signaling pathways involved in this activity, we studied the effects on factor-dependent cell line MO7e cells incubated with SDF-1α alone or in combination with other cytokines. SDF-1α induced transient activation of extracellular stress-regulated kinase (ERK1/2), ribosomal S6 kinase (p9ORSK) and Akt, molecules implicated in cell survival. Moreover, ERK1/2, p90RSK, and Akt were synergistically activated by SDF-1α in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), Steel factor (SLF), or thrombopoietin (TPO). Similar effects were seen after pretreatment of MO7e cells with SDF-1α followed by stimulation with the other cytokines, suggesting a priming effect of SDF-1α. Nuclear factor-ΚB (NF-ΚB) did not appear to be involved in SDF-1α actions, alone or in combination with other cytokines. These intracellular effects were consistent with enhanced myeloid progenitor cell survival by SDF-1α after delayed addition of growth factors. SDF-1α alone supported survival of highly purified human cord blood CD34 +++ cells, less purified human cord blood, and MO7e cells; this effect was synergistically enhanced when SDF-1α was combined with low amounts of other survival-promoting cytokines (GM-CSF, SLF, TPO, and FL). SDF-1 may contribute to maintenance of MPCs in bone marrow by enhancing cell survival alone and in combination with other cytokines.

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