SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on September 4, 2003; DOI 10.1182/blood-2003-04-1115. This Article 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 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. Social Bookmarking                   What's this? Submitted April 10, 2003 Accepted August 28, 2003 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 Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA Microbial, Musculoskeletal and Proliferative Diseases CEDD, GlaxoSmithKline, Collegeville, PA, USA * Corresponding author; email: lpelus{at}iupui.edu. Mobilized peripheral blood stem cells (PBSC) 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 mobilizes PBSC equivalent to G-CSF and are synergistic with G-CSF. We now show that mobilization by GRO/GROT and G-CSF, alone or in combination, requires PMN-derived proteases. GRO/GROT-induced mobilization is associated with elevated 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 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 plasma MMP-9, reduction in marrow NE, CG and MMP-9 and a coincident increase in peripheral blood PMN but decrease in marrow PMN 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 PMN 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: M. J. Christopher, F. Liu, M. J. Hilton, F. Long, and D. C. Link Suppression of CXCL12 production by bone marrow osteoblasts is a common and critical pathway for cytokine-induced mobilization Blood, August 13, 2009; 114(7): 1331 - 1339. [Abstract] [Full Text] [PDF] S. K. Kim, H.-N. Pak, J. H. Park, J. I. Choi, M.-H. Nam, Y. Jo, and Y.-H. Kim Non-ischaemic titrated cardiac injury caused by radiofrequency catheter ablation of atrial fibrillation mobilizes CD34-positive mononuclear cells by non-stromal cell-derived factor-1{alpha} mechanism Europace, August 1, 2009; 11(8): 1024 - 1031. [Abstract] [Full Text] [PDF] N. Smart and P. R. Riley The Stem Cell Movement Circ. Res., May 23, 2008; 102(10): 1155 - 1168. [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] 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] 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] 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]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020