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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 (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 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. Social Bookmarking                   What's this? Submitted August 7, 2002 Accepted February 3, 2003 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 Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA Biochemistry, Molecular Biology and Biophysics, and The Biomedical Engineering Center, University of Minnesota, Minneapolis, MN, USA Molecular Devices, Sunnyvale, CA, USA * Corresponding author; email: dudek002{at}umn.edu. 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 (HPC) with an ED50 of 1 µg/ml but not after exposure to chondroitinase ABC. PF4 enhances adhesion of HPC to intact bone marrow 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 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 (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, seven-transmembrane domain chemokine receptor. Instead, PF4 may modulate the hematopoietic milieu both directly, by promoting progenitor adhesion and quiescence through interaction with a 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: S. Basu and H. E. Broxmeyer CCR5 Ligands Modulate CXCL12-Induced Chemotaxis, Adhesion, and Akt Phosphorylation of Human Cord Blood CD34+ Cells J. Immunol., December 1, 2009; 183(11): 7478 - 7488. [Abstract] [Full Text] [PDF] 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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