CCR5-binding chemokines modulate CXCL 12 (SDF- l)- induced responses of progenitor B cells in human bone marrow through heterologous desensitization of the CXCR4 chemokine receptor

被引:54
作者
Honczarenko, M
Le, Y
Glodek, AM
Majka, M
Campbell, JJ
Ratajczak, MZ
Silberstein, LE
机构
[1] Harvard Univ, Sch Med, Childrens Hosp, Joint Program Transfus Med, Boston, MA 02115 USA
[2] Univ Louisville, James Graham Brown Canc Ctr, Louisville, KY 40292 USA
关键词
D O I
10.1182/blood-2002-01-0248
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Although the SDF-1 (CXCL12)/CXCR4 axis Is Important for B-cell development, It Is not yet clear to what extent CC chemokines might influence B lymphopoiesis. In the current study, we characterized CC chemokine receptor 5 (CCR5) expression and function of primary progenitor B-cell populations in human bone marrow. CCR5 was expressed on all bone marrow B cells at levels between 150 and 200 molecules per cell. Stimulation of bone marrow B cells with the CCR5-binding chemokine macrophage Inflammatory protein 1beta (MIP-1beta; CCL4) did not cause chemotaxis, but CCL4 was able to trigger potent calcium mobilization responses and activation of the mitogen-activated protein kinase (MAPK) pathway in developing B cells. We also determined that CCR5-binding chemokines MIP-1alpha (CCL3), CCL4, and RANTES (CCL5), specifically by signaling through CCR5, could affect all progenitor B-cell populations through a novel mechanism involving heterologous desensitization of CXCR4. This cross-desensitization of CXCR4 was manifested by the inhibition of CXCL12-induced calcium mobilization, MAPK activation, and chemotaxis. These findings indicate that CCR5 can indeed mediate biologic responses of bone marrow B cells, even though these cell populations express low levels of CCR5 on their cell surface. Thus, by modulation of CXCR4 function, signaling through CCR5 may influence B lymphopoiesis by affecting the migration and maturation of B-cell progenitors in the bone marrow microenvironment. (C) 2002 by The American Society of Hematology.
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页码:2321 / 2329
页数:9
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共 39 条
  • [1] Chemoattractant receptor cross-desensitization
    Ali, H
    Richardson, RM
    Haribabu, B
    Snyderman, R
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (10) : 6027 - 6030
  • [2] HIV coreceptor downregulation as antiviral principle: SDF-1 alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication
    Amara, A
    LeGall, S
    Schwartz, O
    Salamero, J
    Montes, M
    Loetscher, P
    Baggiolini, M
    Virelizier, JL
    ArenzanaSeisdedos, F
    [J]. JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (01) : 139 - 146
  • [3] Chemokines in lymphopoiesis and lymphoid organ development
    Ansel, KM
    Cyster, JG
    [J]. CURRENT OPINION IN IMMUNOLOGY, 2001, 13 (02) : 172 - 179
  • [4] Monocyte chemoattractant protein-1-induced CCR2B receptor desensitization mediated by the G protein-coupled receptor kinase 2
    Aragay, AM
    Mellado, M
    Frade, JMR
    Martin, AM
    Jimenez-Sainz, MC
    Martinez-A, C
    Mayor, F
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (06) : 2985 - 2990
  • [5] Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor
    Aramori, I
    Zhang, J
    Ferguson, SSG
    Bieniasz, PD
    Cullen, BR
    Caron, MG
    [J]. EMBO JOURNAL, 1997, 16 (15) : 4606 - 4616
  • [6] Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire
    Campbell, JJ
    Qin, SX
    Unutmaz, D
    Soler, D
    Murphy, KE
    Hodge, MR
    Wu, LJ
    Butcher, EC
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 166 (11) : 6477 - 6482
  • [7] Chemokines - Chemokines and cell migration in secondary lymphoid organs
    Cyster, JG
    [J]. SCIENCE, 1999, 286 (5447) : 2098 - 2102
  • [8] The chemokine SDF-1, stromal cell-derived factor 1, attracts early stage B cell precursors via the chemokine receptor CXCR4
    DApuzzo, M
    Rolink, A
    Loetscher, M
    Hoxie, JA
    ClarkLewis, I
    Melchers, F
    Baggiolini, M
    Moser, B
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 1997, 27 (07) : 1788 - 1793
  • [9] IL-10 induces CCR6 expression during Langerhans cell development while IL-4 and IFN-γ suppress it
    Dieu-Nosjean, MC
    Massacrier, C
    Vanbervliet, B
    Fridman, WH
    Caux, C
    [J]. JOURNAL OF IMMUNOLOGY, 2001, 167 (10) : 5594 - 5602
  • [10] Identification of CXCR4 domains that support coreceptor and chemokine receptor functions
    Doranz, BJ
    Orsini, MJ
    Turner, JD
    Hoffman, TL
    Berson, JF
    Hoxie, JA
    Peiper, SC
    Brass, LF
    Doms, RW
    [J]. JOURNAL OF VIROLOGY, 1999, 73 (04) : 2752 - 2761