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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2002-07-2270. This Article Full Text (PDF) All Versions of this Article: 2002-07-2270v1 103/1/340    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 Velders, G. A Articles by Fibbe, W. E Search for Related Content PubMed PubMed Citation Articles by Velders, G. A Articles by Fibbe, W. E Social Bookmarking                   What's this? Submitted July 26, 2002 Accepted August 14, 2003 Reduced stem cell mobilization in mice receiving antibiotic modulation of the intestinal flora: involvement of endotoxins as cofactors in mobilization Gerjo A Velders, Ronald van Os, Henny Hagoort, Perry Verzaal, Henri F L Guiot, Ivan J D Lindley, Roel Willemze, Ghislain Opdenakker, and Willem E Fibbe* Laboratory of Experimental Hematology, Leiden University Medical Center, Leiden, The Netherlands Laboratory of Medical Microbiology, Leiden University Medical Center, Leiden, The Netherlands Novartis Forschungsinstitut, Vienna, Austria Laboratory for Molecular Immunology, The Rega Institute, Leuven, Belgium * Corresponding author; email: W.E.Fibbe{at}LUMC.nl. Since endotoxins are potent inducers of stem cell mobilization, we hypothesized that their presence in the gut may play a role in cytokine-induced mobilization. To address this possibility we added ciprofloxacin and polymyxin B to the drinking water of Balb/c mice mobilized with either interleukin-8 (IL-8), G-CSF or flt3 ligand (FL). The yield of colony forming units (CFU) was significantly reduced in all mice treated with these antibiotics when compared to controls (IL-8: 192±61 vs. 290±64, p<. 05; G-CSF: 1925±1216 vs. 3371±1214, p<. 05, FL: 562±213 vs. 1068±528, p<. 05). Treatment with ciprofloxacin only eliminated aerobic Gram-negative bacteria from the feces without effect on mobilization. Polymyxin B treatment did not result in decontamination but significantly reduced the number of mobilized progenitor cells (HPC) most likely due to the endotoxin binding capacity of polymyxin B. Over 90% of the gastrointestinal flora consists of anaerobic bacteria. Elimination of the anaerobic flora by metronidazol led to a significantly reduced number of mobilized HPC when compared to controls (IL-8: 55±66 vs. 538±216, p< .05,). Germ-free OF1 mice showed a significantly reduced mobilization compared to their wild type controls (IL-8 controls: 378±182, IL-8 germ free: 157±53, p< .05). Finally, we performed reconstitution experiments adding E. coli derived endotoxins to the drinking water of decontaminated mice. This resulted in partial restoration of the IL-8-induced mobilization (67±28 vs.190±98.1, p<. 01). Our results indicate that endotoxins serve as cofactors in cytokine-induced mobilization. Modification of the endotoxin content by antibiotic treatment may affect the yield of cytokine-induced mobilization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Zuber, I. Radtke, T. S. Pardee, Z. Zhao, A. R. Rappaport, W. Luo, M. E. McCurrach, M.-M. Yang, M. E. Dolan, S. C. Kogan, et al. Mouse models of human AML accurately predict chemotherapy response Genes & Dev., April 1, 2009; 23(7): 877 - 889. [Abstract] [Full Text] [PDF]

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