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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 Hematopoiesis and Stem Cells Chemokines, Cytokines, and Interleukins 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: M. J. Christopher, F. Liu, M. J. Hilton, F. Long, and D. C. 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