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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3682-3690. Prepublished online as a Blood First Edition Paper on August 3, 2006; DOI 10.1182/blood-2006-02-003012. This Article Full Text (PDF) All Versions of this Article: blood-2006-02-003012v1 108/12/3682    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 Panopoulos, A. D Articles by Watowich, S. S Search for Related Content PubMed PubMed Citation Articles by Panopoulos, A. D Articles by Watowich, S. S Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted February 9, 2006 Accepted July 24, 2006 STAT3 governs distinct pathways in emergency granulopoiesis and mature neutrophils Athanasia D Panopoulos, Ling Zhang, Jonathan W Snow, Daniel M Jones, Amber M Smith, Karim C El Kasmi, Fulu Liu, Mark A Goldsmith, Daniel C Link, Peter J Murray, and Stephanie S Watowich* UT MD Anderson Cancer Center; Graduate School of Biomedical Sciences, University of Texas, Houston Gladstone Institute of Virology and Immunology; Harvard Medical School St. Jude Children's Research Hospital, Memphis, TN Washington University School of Medicine, St. Louis, MO Gladstone Institute of Virology and Immunology, San Francisco, CA * Corresponding author; email: swatowic{at}mdanderson.org. Granulocyte colony stimulating factor (G-CSF) is essential for the host response to bacterial infection by controlling neutrophil production in the bone marrow. The G-CSF receptor (G-CSFR) activates the Jak/STAT pathway, although little is understood about how these signals regulate basal and stress-induced granulopoiesis. We examined STAT3 function in granulocytes using a bone marrow conditional knockout mouse model. Our results show that STAT3 has a crucial role in emergency granulopoiesis and mature neutrophil function. STAT3-deficient mice have an aberrant response to G-CSF in vivo, characterized by failure to accumulate immature granulocytes and an increased ratio of mature:immature neutrophils in the bone marrow, peripheral blood and spleen. Acute neutrophil mobilization is impaired in STAT3-deficient mice as judged by their failure to upregulate circulating neutrophils following short term G-CSF exposure. STAT3 also controls neutrophil chemotactic responses to natural ligands for CXCR2, and regulates the magnitude of chemoattractant-induced actin polymerization. These functions of STAT3 are independent of its principal target gene SOCS3, which encodes a crucial feedback inhibitor of cytokine signaling. Our results demonstrate the existence of distinct STAT3 target pathways in neutrophils required for granulopoiesis and innate immunity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Kimura, M. A. Rieger, J. M. Simone, W. Chen, M. C. Wickre, B.-M. Zhu, P. S. Hoppe, J. J. O'Shea, T. Schroeder, and L. Hennighausen The transcription factors STAT5A/B regulate GM-CSF-mediated granulopoiesis Blood, November 19, 2009; 114(21): 4721 - 4728. [Abstract] [Full Text] [PDF] G. D. Jack, L. Zhang, and A. D. Friedman M-CSF elevates c-Fos and phospho-C/EBP{alpha}(S21) via ERK whereas G-CSF stimulates SHP2 phosphorylation in marrow progenitors to contribute to myeloid lineage specification Blood, September 3, 2009; 114(10): 2172 - 2180. [Abstract] [Full Text] [PDF] S. 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