|
|
Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-08-2363.
 Previous Article | Table of Contents | Next Article 
Blood, 15 June 2003, Vol. 101, No. 12, pp. 4687-4694
CHEMOKINES
Platelet factor 4 promotes adhesion of hematopoietic progenitor cells and binds IL-8: novel mechanisms for modulation of hematopoiesis
Arkadiusz Z. Dudek,
Irina Nesmelova,
Kevin Mayo,
Catherine M. Verfaillie,
Simon Pitchford, and
Arne Slungaard
From the Department of Medicine, Division of Hematology, Oncology, and Transplantation, the Stem Cell Institute, and the Departments of Biochemistry, Molecular Biology, and Biophysics, and the Biomedical Engineering Center, University of Minnesota, Minneapolis, MN; and Molecular Devices, Sunnyvale, CA.
Platelet factor 4 (PF4) is an abundant platelet  -granule C-X-C chemokine that has weak chemotactic potency but strongly inhibits hematopoiesis through an unknown mechanism. We find that PF4 binds to human CD34+ hematopoietic progenitor cells (HPCs) with a median effective concentration of 1 µg/mL but not after exposure to chondroitinase ABC. PF4 enhances adhesion of HPCs to intact stroma. Committed progenitors also adhere avidly to immobilized PF4. This adhesion is time-dependent, requires metabolic activity, causes cytoskeletal rearrangement, and induces cell-cycle inhibition. Using extracellular acidification rate to indicate transmembrane signaling, we find that interleukin-8 (IL-8), but not PF4, activates CD34+ progenitors, and PF4 blocks IL-8–mediated activation. Surface plasmon resonance analysis shows that PF4 binds IL-8 with high (dissociation constant [Kd] = 42 nM) affinity. Nuclear magnetic resonance analysis of IL-8 and PF4 in solution confirms this interaction. We conclude that PF4 has the capacity to influence hematopoiesis through mechanisms not mediated by a classical high-affinity, 7-transmembrane domain chemokine receptor. Instead, PF4 may modulate the hematopoietic milieu both directly, by promoting progenitor adhesion and quiescence through interaction with an HPC chondroitin sulfate–containing moiety, and indirectly, by binding to or interfering with signaling caused by other, hematopoietically active chemokines, such as IL-8.
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati What's this?
This article has been cited by other articles:
|
|
|
|
 
Z. Xiao, G. P. Visentin, K. M. Dayananda, and S. Neelamegham
Immune complexes formed following the binding of anti-platelet factor 4 (CXCL4) antibodies to CXCL4 stimulate human neutrophil activation and cell adhesion
Blood,
August 15, 2008;
112(4):
1091 - 1100.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. Cervi, T.-T. Yip, N. Bhattacharya, V. N. Podust, J. Peterson, A. Abou-Slaybi, G. N. Naumov, E. Bender, N. Almog, J. E. Italiano Jr, et al.
Platelet-associated PF-4 as a biomarker of early tumor growth
Blood,
February 1, 2008;
111(3):
1201 - 1207.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Lasagni, R. Grepin, B. Mazzinghi, E. Lazzeri, C. Meini, C. Sagrinati, F. Liotta, F. Frosali, E. Ronconi, N. Alain-Courtois, et al.
PF-4/CXCL4 and CXCL4L1 exhibit distinct subcellular localization and a differentially regulated mechanism of secretion
Blood,
May 15, 2007;
109(10):
4127 - 4134.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Aivado, D. Spentzos, U. Germing, G. Alterovitz, X.-Y. Meng, F. Grall, A. A. N. Giagounidis, G. Klement, U. Steidl, H. H. Otu, et al.
From the cover: Serum proteome profiling detects myelodysplastic syndromes and identifies CXC chemokine ligands 4 and 7 as markers for advanced disease
PNAS,
January 23, 2007;
104(4):
1307 - 1312.
[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]
|
|
|
|
|
|
|
S. E. Crown, Y. Yu, M. D. Sweeney, J. A. Leary, and T. M. Handel
Heterodimerization of CCR2 Chemokines and Regulation by Glycosaminoglycan Binding
J. Biol. Chem.,
September 1, 2006;
281(35):
25438 - 25446.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Paoletti, V. Petkovic, S. Sebastiani, M. G. Danelon, M. Uguccioni, and B. O. Gerber
A rich chemokine environment strongly enhances leukocyte migration and activities
Blood,
May 1, 2005;
105(9):
3405 - 3412.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Weber
Platelets and Chemokines in Atherosclerosis: Partners in Crime
Circ. Res.,
April 1, 2005;
96(6):
612 - 616.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. V. Nesmelova, Y. Sham, A. Z. Dudek, L. I. van Eijk, G. Wu, A. Slungaard, F. Mortari, A. W. Griffioen, and K. H. Mayo
Platelet Factor 4 and Interleukin-8 CXC Chemokine Heterodimer Formation Modulates Function at the Quaternary Structural Level
J. Biol. Chem.,
February 11, 2005;
280(6):
4948 - 4958.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. von Hundelshausen, R. R. Koenen, M. Sack, S. F. Mause, W. Adriaens, A. E. I. Proudfoot, T. M. Hackeng, and C. Weber
Heterophilic interactions of platelet factor 4 and RANTES promote monocyte arrest on endothelium
Blood,
February 1, 2005;
105(3):
924 - 930.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Emadi, D. Clay, C. Desterke, B. Guerton, E. Maquarre, A. Charpentier, C. Jasmin, M.-C. Le Bousse-Kerdiles, and for the French INSERM Research Network on MMM
IL-8 and its CXCR1 and CXCR2 receptors participate in the control of megakaryocytic proliferation, differentiation, and ploidy in myeloid metaplasia with myelofibrosis
Blood,
January 15, 2005;
105(2):
464 - 473.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Struyf, M. D. Burdick, P. Proost, J. Van Damme, and R. M. Strieter
Platelets Release CXCL4L1, a Nonallelic Variant of the Chemokine Platelet Factor-4/CXCL4 and Potent Inhibitor of Angiogenesis
Circ. Res.,
October 29, 2004;
95(9):
855 - 857.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
