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

Research output: Contribution to journalArticle

130 Scopus citations

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

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Lee, Y., Gotoh, A., Kwon, H. J., You, M., Kohli, L., Mantel, C., Cooper, S., Hangoc, G., Miyazawa, K., Ohyashiki, K., & Broxmeyer, H. E. (2002). Enhancement of intracellular signaling associated with hematopoietic progenitor cell survival in response to SDF-1/CXCL12 in synergy with other cytokines. Blood, 99(12), 4307-4317. https://doi.org/10.1182/blood.V99.12.4307