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Blood, 15 July 2004, Vol. 104, No. 2, pp. 565-571. Prepublished online as a Blood First Edition Paper on April 6, 2004March 30, 2004; DOI 10.1182/blood-2003-10-3638. This Article Full Text (PDF) All Versions of this Article: 2003-10-3638v1 2003-10-3638v2 104/2/565    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 Suratt, B. T Articles by Worthen, G S Search for Related Content PubMed PubMed Citation Articles by Suratt, B. T Articles by Worthen, G S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 24, 2003 Accepted March 9, 2004 The role of the CXCR4/SDF-1 chemokine axis in circulating neutrophil homeostasis Benjamin T Suratt*, Joseph M Petty, Scott K Young, Kenneth C Malcolm, Jonathan G Lieber, Jerry A Nick, Jose-Angel Gonzalo, Peter M Henson, and G S Worthen Medicine, University of Vermont College of Medicine, Burlington, VT, USA Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA Medicine, National Jewish Medical and Research Center, Denver, CO, USA Medicine, National Jewish Medical and Research Center, Denver, CO, USA; Medicine, University of Colorado Health Sciences Center, Denver, CO, USA Millennium Pharmaceuticals, Inc., Cambridge, MA, USA Pediatrics, National Jewish Medical and Research Center, Denver, CO, USA; Pathology, University of Colorado Health Sciences Center, Denver, CO, USA * Corresponding author; email: benjamin.suratt{at}uvm.edu. The bone marrow is not only recognized as the primary site for the release of neutrophils, but also may function in their selective retention from neutrophil production and release into the circulation. Since the CXCR4/SDF-1 axis plays a central role in the interactions of hematopoietic stem cells, lymphocytes, and developing neutrophils in the marrow, we investigated whether reciprocal CXCR4-dependent mechanisms might be involved in neutrophil release and subsequent return to the marrow following circulation. Neutralizing antibody to CXCR4 reduced marrow-retention of infused neutrophils (45.7±0.5% to 6.9±0.5%), and was found to mobilize neutrophils from marrow (34.4 ±4.4%). Neutrophil CXCR4-expression and SDF-1-induced calcium flux decreased with maturation and activation of the cells, corresponding to the decreased marrow-homing associated with these characteristics in vivo. Infusion of the inflammatory mediator and CXCR2 ligand KC led to mobilization of neutrophils from marrow by itself, and was augmented three-fold by low doses of CXCR4-blocking antibody that otherwise had no mobilizing effect. Examination of KC and SDF-1 calcium-signaling demonstrated that KC's effects may, in part, be due to heterologous desensitization to SDF-1. These results suggest that the CXCR4/SDF-1 axis is critical in circulating neutrophil homeostasis, and that it may participate in the rapid release of neutrophils from the marrow during inflammation through a novel interaction with inflammatory CXC chemokines. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: K. Hochweller, T. Miloud, J. Striegler, S. Naik, G. J. Hammerling, and N. 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