SEARCH:   Advanced

Blood, 1 January 2004, Vol. 103, No. 1, pp. 110-119. Prepublished online as a Blood First Edition Paper on September 4, 2003; DOI 10.1182/blood-2003-04-1115. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-04-1115v1 103/1/110    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 Pelus, L. M. Articles by Fukuda, S. Search for Related Content PubMed PubMed Citation Articles by Pelus, L. M. Articles by Fukuda, S. Related Collections Chemokines, Cytokines, and Interleukins Hematopoiesis and Stem Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Neutrophil-derived MMP-9 mediates synergistic mobilization of hematopoietic stem and progenitor cells by the combination of G-CSF and the chemokines GRO/CXCL2 and GROT /CXCL24 Louis M. Pelus, Huimin Bian, Andrew G. King, and Seiji Fukuda From the Department of Microbiology and Immunology and the Walther Oncology Center, Indiana University School of Medicine, and the Walther Cancer Institute, Indianapolis, IN; and the Microbial, Musculoskeletal and Proliferative Diseases Centers of Excellence in Drug Discovery (CEDD), GlaxoSmithKline, Collegeville, PA. Mobilized peripheral blood stem cells (PBSCs) are widely used for transplantation, but mechanisms mediating their release from marrow are poorly understood. We previously demonstrated that the chemokines GRO/CXCL2 and GROT/CXCL24 rapidly mobilize PBSC equivalent to granulocyte colony-stimulating factor (G-CSF) and are synergistic with G-CSF. We now show that mobilization by GRO/GROT and G-CSF, alone or in combination, requires polymorphonuclear neutrophil (PMN)–derived proteases. Mobilization induced by GRO/GROT is associated with elevated levels of plasma and marrow matrix metalloproteinase 9 (MMP-9) and mobilization and MMP-9 are absent in neutrophil-depleted mice. G-CSF mobilization correlates with elevated neutrophil elastase (NE), cathepsin G (CG), and MMP-9 levels within marrow and is partially blocked by either anti–MMP-9 or the NE inhibitor MeOSuc-Ala-Ala-Pro-Val-CMK. Mobilization and protease accumulation are absent in neutrophil-depleted mice. Synergistic PBSC mobilization observed when G-CSF and GRO/GROT are combined correlates with a synergistic rise in the level of plasma MMP-9, reduction in marrow NE, CG, and MMP-9 levels, and a coincident increase in peripheral blood PMNs but decrease in marrow PMNs compared to G-CSF. Synergistic mobilization is completely blocked by anti–MMP-9 but not MeOSuc-Ala-Ala-Pro-Val-CMK and absent in MMP-9–deficient or PMN-depleted mice. Our results indicate that PMNs are a common target for G-CSF and GRO/GROT-mediated PBSC mobilization and, importantly, that synergistic mobilization by G-CSF plus GRO/GROT is mediated by PMN-derived plasma MMP-9. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. Smart and P. R. Riley The Stem Cell Movement Circ. Res., May 23, 2008; 102(10): 1155 - 1168. [Abstract] [Full Text] [PDF] D. E. Cramer, S. Wagner, B. Li, J. Liu, R. Hansen, R. Reca, W. Wu, E. Z. Surma, D. A. Laber, M. Z. Ratajczak, et al. Mobilization of Hematopoietic Progenitor Cells by Yeast-Derived {beta}-Glucan Requires Activation of Matrix Metalloproteinase-9 Stem Cells, May 1, 2008; 26(5): 1231 - 1240. [Abstract] [Full Text] [PDF] T. Papayannopoulou and D. T. Scadden Stem-cell ecology and stem cells in motion Blood, April 15, 2008; 111(8): 3923 - 3930. [Abstract] [Full Text] [PDF] M. van Pel, H. Hagoort, M. J. Kwakkenbos, J. Hamann, and W. E. Fibbe Differential role of CD97 in interleukin-8-induced and granulocyte-colony stimulating factor-induced hematopoietic stem and progenitor cell mobilization Haematologica, April 1, 2008; 93(4): 601 - 604. [Abstract] [Full Text] [PDF] J.-P. Levesque, I. G. Winkler, J. Hendy, B. Williams, F. Helwani, V. Barbier, B. Nowlan, and S. K. Nilsson Hematopoietic Progenitor Cell Mobilization Results in Hypoxia with Increased Hypoxia-Inducible Transcription Factor-1{alpha} and Vascular Endothelial Growth Factor A in Bone Marrow Stem Cells, August 1, 2007; 25(8): 1954 - 1965. [Abstract] [Full Text] [PDF] S. Fukuda, H. Bian, A. G. King, and L. M. Pelus The chemokine GRO{beta} mobilizes early hematopoietic stem cells characterized by enhanced homing and engraftment Blood, August 1, 2007; 110(3): 860 - 869. [Abstract] [Full Text] [PDF] R. A. Panepucci, R. T. Calado, V. Rocha, R. Proto-Siqueira, W. A. Silva Jr., and M. A. Zago Higher Expression of Transcription Targets and Components of the Nuclear Factor-{kappa}B Pathway Is a Distinctive Feature of Umbilical Cord Blood CD34+ Precursors Stem Cells, January 1, 2007; 25(1): 189 - 196. [Abstract] [Full Text] [PDF] C. Carlo-Stella, M. Di Nicola, P. Longoni, L. Cleris, C. Lavazza, R. Milani, M. Milanesi, M. Magni, V. Pace, F. Colotta, et al. Placental Growth Factor-1 Potentiates Hematopoietic Progenitor Cell Mobilization Induced by Granulocyte Colony-Stimulating Factor in Mice and Nonhuman Primates Stem Cells, January 1, 2007; 25(1): 252 - 261. [Abstract] [Full Text] [PDF] C. Selleri, N. Montuori, P. Ricci, V. Visconte, A. Baiano, M. V. Carriero, B. Rotoli, G. Rossi, and P. Ragno In vivo Activity of the Cleaved Form of Soluble Urokinase Receptor: A New Hematopoietic Stem/Progenitor Cell Mobilizer. Cancer Res., November 15, 2006; 66(22): 10885 - 10890. [Abstract] [Full Text] [PDF] A. Tefferi Pathogenesis of Myelofibrosis With Myeloid Metaplasia J. Clin. Oncol., November 20, 2005; 23(33): 8520 - 8530. [Abstract] [Full Text] [PDF] Y. Guo, G. Hangoc, H. Bian, L. M. Pelus, and H. E. Broxmeyer SDF-1/CXCL12 Enhances Survival and Chemotaxis of Murine Embryonic Stem Cells and Production of Primitive and Definitive Hematopoietic Progenitor Cells Stem Cells, September 1, 2005; 23(9): 1324 - 1332. [Abstract] [Full Text] [PDF] S. Fukuda, H. E. Broxmeyer, and L. M. Pelus Flt3 ligand and the Flt3 receptor regulate hematopoietic cell migration by modulating the SDF-1{alpha}(CXCL12)/CXCR4 axis Blood, April 15, 2005; 105(8): 3117 - 3126. [Abstract] [Full Text] [PDF] C. Selleri, N. Montuori, P. Ricci, V. Visconte, M. V. Carriero, N. Sidenius, B. Serio, F. Blasi, B. Rotoli, G. Rossi, et al. Involvement of the urokinase-type plasminogen activator receptor in hematopoietic stem cell mobilization Blood, March 1, 2005; 105(5): 2198 - 2205. [Abstract] [Full Text] [PDF] T. Papayannopoulou Current mechanistic scenarios in hematopoietic stem/progenitor cell mobilization Blood, March 1, 2004; 103(5): 1580 - 1585. [Abstract] [Full Text] [PDF] S. O'Brien, A. Tefferi, and P. Valent Chronic Myelogenous Leukemia and Myeloproliferative Disease Hematology, January 1, 2004; 2004(1): 146 - 162. [Abstract] [Full Text] [PDF]

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020