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Prepublished online as a Blood First Edition Paper on February 13, 2003; DOI 10.1182/blood-2002-08-2363. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-08-2363v1 101/12/4687    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dudek, A. Z. Articles by Slungaard, A. Search for Related Content PubMed PubMed Citation Articles by Dudek, A. Z. Articles by Slungaard, A. Related Collections Hematopoiesis and Stem Cells Cell Cycle Cell Adhesion and Motility Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  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: E. C. Keeley, B. Mehrad, and R. M. Strieter Chemokines as Mediators of Neovascularization Arterioscler Thromb Vasc Biol, November 1, 2008; 28(11): 1928 - 1936. [Abstract] [Full Text] [PDF] M. C. Picchio, E. Scala, D. Pomponi, E. Caprini, M. Frontani, I. Angelucci, A. Mangoni, C. Lazzeri, M. Perez, D. Remotti, et al. 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