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

被引:116
作者
Lee, Y
Gotoh, A
Kwon, HJ
You, M
Kohli, L
Mantel, C
Cooper, S
Hangoc, G
Miyazawa, K
Ohyashiki, K
Broxmeyer, HE
机构
[1] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA
[2] Indiana Univ, Sch Med, Dept Microbiol Immunol, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA
[4] Indiana Univ, Sch Med, Dept Biochem, Indianapolis, IN 46202 USA
[5] Indiana Univ, Sch Med, Dept Mol Biol, Indianapolis, IN 46202 USA
[6] Walther Canc Inst, Indianapolis, IN USA
[7] Tokyo Med Univ, Dept Internal Med 1, Shinjuku Ku, Tokyo, Japan
关键词
D O I
10.1182/blood.V99.12.4307
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Stromal cell-derived factor 1 (SDF-1/ CXCL12) is a multifunctional cytokine. We previously reported that myelopoiesis was enhanced in SDF-1alpha. transgenic mice, probably due in part to SDF-1a 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-1alpha alone or in combination with other cytokines. SDF-1alpha induced transient activation of extracellular stress-regulated kinase (ERK1/2), ribosomal S6 kinase (p9ORSK) and Akt, molecules implicated in cell survival. Moreover, ERK1/2, p9ORSK, and Akt were synergistically activated by SDF-1alpha in combination with granulocyte-macrophage colony-stimulating factor (GMCSF), Steel factor (SLF), or thrombopoietin (TPO). Similar effects were seen after pretreatment of MO7e cells with SDF-1alpha followed by stimulation with the other cytokines, suggesting a priming effect of SDF-1alpha. Nuclear factor-kappaB (NF-kappaB) did not appear to be involved in SDF-1alpha actions, alone or in combination with other cytokines. These intracellular effects were consistent with enhanced myeloid progenitor cell survival by SDF-1alpha. after delayed addition of growth factors. SDF-1alpha, 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-1alpha a 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. (Blood. 2002;99:4307-4317) (C) 2002 by The American Society of Hematology.
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收藏
页码:4307 / 4317
页数:11
相关论文
共 73 条
  • [1] The chemokine SDF-1 is a chemoattractant for human CD34(+) hematopoietic progenitor cells and provides a new mechanism to explain the mobilization of CD34(+) progenitors to peripheral blood
    Aiuti, A
    Webb, IJ
    Bleul, C
    Springer, T
    GutierrezRamos, JC
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 185 (01) : 111 - 120
  • [2] SELECTIVE GROWTH-RESPONSE TO IL-3 OF A HUMAN-LEUKEMIC CELL-LINE WITH MEGAKARYOBLASTIC FEATURES
    AVANZI, GC
    LISTA, P
    GIOVINAZZO, B
    MINIERO, R
    SAGLIO, G
    BENETTON, G
    CODA, R
    CATTORETTI, G
    PEGORARO, L
    [J]. BRITISH JOURNAL OF HAEMATOLOGY, 1988, 69 (03) : 359 - 366
  • [3] Signal transduction, cell cycle regulatory, and anti-apoptotic pathways regulated by IL-3 in hematopoietic cells: possible sites for intervention with anti-neoplastic drugs
    Blalock, WL
    Weinstein-Oppenheimer, C
    Chang, F
    Hoyle, PE
    Wang, XY
    Algate, PA
    Franklin, RA
    Oberhaus, SM
    Steelman, LS
    McCubrey, JA
    [J]. LEUKEMIA, 1999, 13 (08) : 1109 - 1166
  • [4] GROWTH-CHARACTERISTICS AND EXPANSION OF HUMAN UMBILICAL-CORD BLOOD AND ESTIMATION OF ITS POTENTIAL FOR TRANSPLANTATION IN ADULTS
    BROXMEYER, HE
    HANGOC, G
    COOPER, S
    RIBEIRO, RC
    GRAVES, V
    YODER, M
    WAGNER, J
    VADHANRAJ, S
    BENNINGER, L
    RUBINSTEIN, P
    BROUN, ER
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (09) : 4109 - 4113
  • [5] Broxmeyer HE, 1999, BLOOD, V94, p650A
  • [6] Regulation of hematopoiesis in a sea of chemokine family members with a plethora of redundant activities
    Broxmeyer, HE
    Kim, CH
    [J]. EXPERIMENTAL HEMATOLOGY, 1999, 27 (07) : 1113 - 1123
  • [7] Burger JA, 2000, BLOOD, V96, P2655
  • [8] Colamussi ML, 2001, J LEUKOCYTE BIOL, V69, P263
  • [9] COOPER S, 1996, CURRENT PROTOCOLS S, V18
  • [10] Cellular survival: a play in three Akts
    Datta, SR
    Brunet, A
    Greenberg, ME
    [J]. GENES & DEVELOPMENT, 1999, 13 (22) : 2905 - 2927