SEARCH:   Advanced

Blood, 1 July 2004, Vol. 104, No. 1, pp. 65-72. Prepublished online as a Blood First Edition Paper on March 9, 2004; DOI 10.1182/blood-2003-05-1589. This Article Full Text (PDF) All Versions of this Article: 2003-05-1589v1 104/1/65    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 Levesque, J.-P. Articles by Link, D. C Search for Related Content PubMed PubMed Citation Articles by Levesque, J.-P. Articles by Link, D. C Social Bookmarking                   What's this? Next Article  Submitted May 16, 2003 Accepted February 26, 2004 Characterization of Hematopoietic Progenitor Mobilization in Protease Deficient Mice Jean-Pierre Levesque, Fulu Liu, Paul J Simmons, Tomoko Betsuyaku, Robert Senior, Christine Pham, and Daniel C Link* Oncology, Washington University, St. Louis, MO, USA Pulmonary and Critical Care Medicine, Washington University, St. Louis, MO, USA Rheumatology, Washington University, St. Louis, MO, USA Stem Cell Biology Laboratory, Peter MacCallum Cancer Institute, Victoria, Austria First Department of Medicine, Hokkaido University School of Medicine, Sapparo, Japan * Corresponding author; email: dlink{at}im.wustl.edu. Recent evidence suggests that protease release by neutrophils in the bone marrow may contribute to hematopoietic progenitor cell (HPC) mobilization. Matrix metalloproteinase-9 (MMP-9), neutrophil elastase (NE) and cathepsin G (CG) accumulate in the bone marrow during G-CSF treatment, where they are thought to degrade key substrates including vascular cell adhesion molecule-1 (VCAM-1) and CXCL12. To test this hypothesis, HPC mobilization was characterized in transgenic mice deficient in one or more hematopoietic protease. Surprisingly, HPC mobilization by G-CSF was normal in MMP-9 deficient mice, NExCG deficient mice, or mice lacking dipeptidyl peptidase I, an enzyme required for the functional activation of many hematopoietic serine proteases. Moreover, combined inhibition of neutrophil serine proteases and metalloproteinases had no significant effect on HPC mobilization. VCAM-1 expression on bone marrow stromal cells decreased during G-CSF treatment of wild type mice but not NExCG deficient mice, indicating that VCAM-1 cleavage is not required for efficient HPC mobilization. G-CSF induced a significant decrease in CXCL12 protein expression in the bone marrow of NExCG deficient mice, indicating that these proteases are not required to down-regulate CXCL12 expression. Collectively, these data suggest a complex model in which both protease-dependent and independent pathways may contribute to HPC mobilization. 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] K. Horiuchi, T. Kimura, T. Miyamoto, K. Miyamoto, H. Akiyama, H. Takaishi, H. Morioka, T. Nakamura, Y. Okada, C. P. Blobel, et al. Conditional Inactivation of TACE by a Sox9 Promoter Leads to Osteoporosis and Increased Granulopoiesis via Dysregulation of IL-17 and G-CSF J. Immunol., February 15, 2009; 182(4): 2093 - 2101. [Abstract] [Full Text] [PDF] M. Tjwa, S. Janssens, and P. Carmeliet Plasmin therapy enhances mobilization of HPCs after G-CSF Blood, November 15, 2008; 112(10): 4048 - 4050. [Abstract] [Full Text] [PDF] S. von Vietinghoff and K. Ley Homeostatic Regulation of Blood Neutrophil Counts J. Immunol., October 15, 2008; 181(8): 5183 - 5188. [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] A. M. Wengner, S. C. Pitchford, R. C. Furze, and S. M. Rankin The coordinated action of G-CSF and ELR + CXC chemokines in neutrophil mobilization during acute inflammation Blood, January 1, 2008; 111(1): 42 - 49. [Abstract] [Full Text] [PDF] H. K. Kim, M. De La Luz Sierra, C. K. Williams, A. V. Gulino, and G. Tosato G-CSF down-regulation of CXCR4 expression identified as a mechanism for mobilization of myeloid cells Blood, August 1, 2006; 108(3): 812 - 820. [Abstract] [Full Text] [PDF] E. A. Copelan Hematopoietic stem-cell transplantation. N. Engl. J. Med., April 27, 2006; 354(17): 1813 - 1826. [Full Text] [PDF] C. L. Semerad, M. J. Christopher, F. Liu, B. Short, P. J. Simmons, I. Winkler, J.-P. Levesque, J. Chappel, F. P. Ross, and D. C. Link G-CSF potently inhibits osteoblast activity and CXCL12 mRNA expression in the bone marrow Blood, November 1, 2005; 106(9): 3020 - 3027. [Abstract] [Full Text] [PDF] H.-G. Kopp, S. T. Avecilla, A. T. Hooper, and S. Rafii The Bone Marrow Vascular Niche: Home of HSC Differentiation and Mobilization Physiology, October 1, 2005; 20(5): 349 - 356. [Abstract] [Full Text] [PDF] T. Ulyanova, L. M. Scott, G. V. Priestley, Y. Jiang, B. Nakamoto, P. A. Koni, and T. Papayannopoulou VCAM-1 expression in adult hematopoietic and nonhematopoietic cells is controlled by tissue-inductive signals and reflects their developmental origin Blood, July 1, 2005; 106(1): 86 - 94. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020