|
|
 Previous Article | Table of Contents | Next Article 
Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1511-1523
Phenotypic and Functional Evidence for the Expression of CXCR4
Receptor During Megakaryocytopoiesis
Christel Rivière,
Frédéric Subra,
Karine Cohen-Solal,
Véronique Cordette-Lagarde,
Remi Letestu,
Christian Auclair,
William Vainchenker, and
Fawzia Louache
From the INSERM U 362, Institut Gustave Roussy; and CNRS URA 147, Institut Gustave Roussy, Villejuif, France.
The identification of stromal cell-derived factor (SDF)-1 as a
chemoattractant for human progenitor cells suggests that this chemokine
and its receptor might represent critical determinants for the homing,
retention, and exit of precursor cells from hematopoietic organs. In
this study, we investigated the expression profile of CXCR4 receptor
and the biological activity of SDF-1 during megakaryocytopoiesis. CD34+ cells from bone marrow and
cord blood were purified and induced to differentiate toward the
megakaryocyte lineage by a combination of stem-cell factor (SCF) and
recombinant human pegylated megakaryocyte growth and development factor
(PEG-rhuMGDF). After 6 days of culture, a time where mature and
immature megakaryocytes were present, CD41+ cells were
immunopurified and CXCR4mRNA expression was studied. High transcript
levels were detected by a RNase protection assay in cultured
megakaryocytes derived from cord blood CD34+ cells as
well as in peripheral blood platelets. The transcript levels were about
equivalent to that found in activated T cells. By flow cytometry, a
large fraction (ranging from 30% to 100%) of CD41+
cells showed high levels of CXCR4 antigen on their surface, its expression increasing in parallel with the CD41 antigen during megakaryocytic differentiation. CXCR4 protein was also detected on
peripheral blood platelets. SDF-1 acts on megakaryocytes by inducing
intracellular calcium mobilization and actin polymerization. In
addition, in in vitro transmigration experiments, a significant proportion of megakaryocytes was observed to respond to this chemokine. This cell migration was inhibited by pertussis toxin, indicating coupling of this signal to heterotrimeric guanine nucleotide binding proteins. Although a close correlation between CD41a and CXCR4 expession was observed, cell surface markers as well as morphological criteria indicate a preferential attraction of immature megakaryocytes (low level of CD41a and CD42a), suggesting that SDF-1 is a potent attractant for immature megakaryocytic cells but is less active on
fully mature megakaryocytes. This hypothesis was further supported by
the observation that SDF-1 induced the migration of colony forming
unit-megakaryocyte progenitors (CFU-MK) and the expression of
activation-dependent P-selectin (CD62P) surface antigen on early
megakaryocytes, although no effect was observed on mature megakaryocytes and platelets. These results indicate that CXCR4 is
expressed by human megakaryocytes and platelets. Furthermore, based on
the lower responses of mature megakaryocytes and platelets to SDF-1
as compared with early precursors, these data suggest a role for this
chemokine in the maintenance and homing during early stages of
megakaryocyte development. Moreover, because megakaryocytes are also
reported to express CD4, it becomes important to reevaluate the role of
direct infection of these cells by the human immunodeficiency virus
(HIV)-1 in HIV-1-related thrombocytopenia.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
L. Gilles, D. Bluteau, S. Boukour, Y. Chang, Y. Zhang, T. Robert, P. Dessen, N. Debili, O. A. Bernard, W. Vainchenker, et al.
MAL/SRF complex is involved in platelet formation and megakaryocyte migration by regulating MYL9 (MLC2) and MMP9
Blood,
November 5, 2009;
114(19):
4221 - 4232.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Yang, M. Koupenova, D. J. McCrann, K. J. Kopeikina, H. M. Kagan, B. M. Schreiber, and K. Ravid
The A2b adenosine receptor protects against vascular injury
PNAS,
January 15, 2008;
105(2):
792 - 796.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Jin, Y. Tabe, S. Konoplev, Y. Xu, C. E. Leysath, H. Lu, S. Kimura, A. Ohsaka, M.-B. Rios, L. Calvert, et al.
CXCR4 up-regulation by imatinib induces chronic myelogenous leukemia (CML) cell migration to bone marrow stroma and promotes survival of quiescent CML cells
Mol. Cancer Ther.,
January 1, 2008;
7(1):
48 - 58.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. S. Dhanjal, C. Pendaries, E. A. Ross, M. K. Larson, M. B. Protty, C. D. Buckley, and S. P. Watson
A novel role for PECAM-1 in megakaryocytokinesis and recovery of platelet counts in thrombocytopenic mice
Blood,
May 15, 2007;
109(10):
4237 - 4244.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. von Hundelshausen and C. Weber
Platelets as Immune Cells: Bridging Inflammation and Cardiovascular Disease
Circ. Res.,
January 5, 2007;
100(1):
27 - 40.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Berthebaud, C. Riviere, P. Jarrier, A. Foudi, Y. Zhang, D. Compagno, A. Galy, W. Vainchenker, and F. Louache
RGS16 is a negative regulator of SDF-1-CXCR4 signaling in megakaryocytes
Blood,
November 1, 2005;
106(9):
2962 - 2968.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Mondal, C. A. Williams, M. Ali, M. Eilers, and K. C. Agrawal
The HIV-1 Tat Protein Selectively Enhances CXCR4 and Inhibits CCR5 Expression in Megakaryocytic K562 Cells
Experimental Biology and Medicine,
October 1, 2005;
230(9):
631 - 644.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J.-F. Geay, D. Buet, Y. Zhang, A. Foudi, P. Jarrier, M. Berthebaud, A. G. Turhan, W. Vainchenker, and F. Louache
p210BCR-ABL inhibits SDF-1 Chemotactic Response via Alteration of CXCR4 Signaling and Down-regulation of CXCR4 Expression
Cancer Res.,
April 1, 2005;
65(7):
2676 - 2683.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. S. Li, A. Forslow, and K.-G. Sundqvist
Autocrine Regulation of T Cell Motility by Calreticulin-Thrombospondin-1 Interaction
J. Immunol.,
January 15, 2005;
174(2):
654 - 661.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Schafer, C. Schulz, M. Eigenthaler, D. Fraccarollo, A. Kobsar, M. Gawaz, G. Ertl, U. Walter, and J. Bauersachs
Novel role of the membrane-bound chemokine fractalkine in platelet activation and adhesion
Blood,
January 15, 2004;
103(2):
407 - 412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. D. van Buul, C. Voermans, J. van Gelderen, E. C. Anthony, C. E. van der Schoot, and P. L. Hordijk
Leukocyte-Endothelium Interaction Promotes SDF-1-dependent Polarization of CXCR4
J. Biol. Chem.,
August 8, 2003;
278(32):
30302 - 30310.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Youssefian, A. Drouin, J.-M. Masse, J. Guichard, and E. M. Cramer
Host defense role of platelets: engulfment of HIV and Staphylococcus aureus occurs in a specific subcellular compartment and is enhanced by platelet activation
Blood,
May 13, 2002;
99(11):
4021 - 4029.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Fruehauf, K. Srbic, R. Seggewiss, J. Topaly, and A. D. Ho
Functional characterization of podia formation in normal and malignant hematopoietic cells
J. Leukoc. Biol.,
March 1, 2002;
71(3):
425 - 432.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
G. Mattia, F. Vulcano, L. Milazzo, A. Barca, G. Macioce, A. Giampaolo, and H. J. Hassan
Different ploidy levels of megakaryocytes generated from peripheral or cord blood CD34+ cells are correlated with different levels of platelet release
Blood,
February 1, 2002;
99(3):
888 - 897.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Hattori, B. Heissig, K. Tashiro, T. Honjo, M. Tateno, J.-H. Shieh, N. R. Hackett, M. S. Quitoriano, R. G. Crystal, S. Rafii, et al.
Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells
Blood,
June 1, 2001;
97(11):
3354 - 3360.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Guerriero, G. Mattia, U. Testa, C. Chelucci, G. Macioce, I. Casella, P. Samoggia, C. Peschle, and H. J. Hassan
Stromal cell-derived factor 1{alpha} increases polyploidization of megakaryocytes generated by human hematopoietic progenitor cells
Blood,
May 1, 2001;
97(9):
2587 - 2595.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. R. L. Gear, S. Suttitanamongkol, D. Viisoreanu, R. K. Polanowska-Grabowska, S. Raha, and D. Camerini
Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function
Blood,
February 15, 2001;
97(4):
937 - 945.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Majka, A. Janowska-Wieczorek, J. Ratajczak, M. A. Kowalska, G. Vilaire, Z. K. Pan, M. Honczarenko, L. A. Marquez, M. Poncz, and M. Z. Ratajczak
Stromal-derived factor 1 and thrombopoietin regulate distinct aspects of human megakaryopoiesis
Blood,
December 15, 2000;
96(13):
4142 - 4151.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. J. Lane, S. Dias, K. Hattori, B. Heissig, M. Choy, S. Y. Rabbany, J. Wood, M. A. S. Moore, and S. Rafii
Stromal-derived factor 1-induced megakaryocyte migration and platelet production is dependent on matrix metalloproteinases
Blood,
December 15, 2000;
96(13):
4152 - 4159.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Krzysiek, E. A. Lefevre, J. Bernard, A. Foussat, P. Galanaud, F. Louache, and Y. Richard
Regulation of CCR6 chemokine receptor expression and responsiveness to macrophage inflammatory protein-3alpha /CCL20 in human B cells
Blood,
October 1, 2000;
96(7):
2338 - 2345.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. A. Kowalska, M. Z. Ratajczak, M. Majka, J. Jin, S. Kunapuli, L. Brass, and M. Poncz
Stromal cell-derived factor-1 and macrophage-derived chemokine: 2 chemokines that activate platelets
Blood,
July 1, 2000;
96(1):
50 - 57.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Shiraga, A. Ritchie, S. Aidoudi, V. Baron, D. Wilcox, G. White, B. Ybarrondo, G. Murphy, A. Leavitt, and S. Shattil
Primary Megakaryocytes Reveal a Role for Transcription Factor Nf-E2 in Integrin {alpha}iib{beta}3 Signaling
J. Cell Biol.,
December 27, 1999;
147(7):
1419 - 1430.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Chelucci, I. Casella, M. Federico, U. Testa, G. Macioce, E. Pelosi, R. Guerriero, G. Mariani, A. Giampaolo, H.J. Hassan, et al.
Lineage-Specific Expression of Human Immunodeficiency Virus (HIV) Receptor/Coreceptors in Differentiating Hematopoietic Precursors: Correlation With Susceptibility to T- and M-Tropic HIV and Chemokine-Mediated HIV Resistance
Blood,
September 1, 1999;
94(5):
1590 - 1600.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Haddad, E. Cramer, C. Riviere, P. Rameau, F. Louache, J. Guichard, D. L. Nelson, A. Fischer, W. Vainchenker, and N. Debili
The Thrombocytopenia of Wiskott Aldrich Syndrome Is Not Related to a Defect in Proplatelet Formation
Blood,
July 15, 1999;
94(2):
509 - 518.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
