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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 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 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 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. Related Collections Hematopoiesis and Stem Cells Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS 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 From the Department of Immunology, The University of Texas M. D. Anderson Cancer Center, Houston; Department of Hematopathology, The University of Texas M. D. Anderson Cancer Center, Houston; Graduate School of Biomedical Sciences, University of Texas, Houston; Gladstone Institute of Virology and Immunology, San Francisco, CA; Department of Hematology and Oncology, Children's Hospital Boston, Harvard Medical School, MA; Department of Infectious Diseases, St Jude Children's Research Hospital, Memphis, TN; and Department of Internal Medicine, Washington University School of Medicine, St Louis, MO. 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 to 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 up-regulate 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: K.-H. Chuang, S. Altuwaijri, G. Li, J.-J. Lai, C.-Y. Chu, K.-P. Lai, H.-Y. Lin, J.-W. Hsu, P. Keng, M.-C. Wu, et al. Neutropenia with impaired host defense against microbial infection in mice lacking androgen receptor J. Exp. Med., May 11, 2009; 206(5): 1181 - 1199. [Abstract] [Full Text] [PDF] K. Speiran, D. P. Bailey, J. Fernando, M. Macey, B. Barnstein, M. Kolawole, D. Curley, S. S. Watowich, P. J. Murray, C. Oskeritzian, et al. Endogenous suppression of mast cell development and survival by IL-4 and IL-10 J. Leukoc. Biol., May 1, 2009; 85(5): 826 - 836. [Abstract] [Full Text] [PDF] D. A. Steimer, K. Boyd, O. Takeuchi, J. K. Fisher, G. P. Zambetti, and J. T. Opferman Selective roles for antiapoptotic MCL-1 during granulocyte development and macrophage effector function Blood, March 19, 2009; 113(12): 2805 - 2815. [Abstract] [Full Text] [PDF] B. J. van Raam, A. Drewniak, V. Groenewold, T. K. van den Berg, and T. W. Kuijpers Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3 Blood, September 1, 2008; 112(5): 2046 - 2054. [Abstract] [Full Text] [PDF] L. J. Quinton, M. R. Jones, B. E. Robson, B. T. Simms, J. A. Whitsett, and J. P. Mizgerd Alveolar Epithelial STAT3, IL-6 Family Cytokines, and Host Defense during Escherichia coli Pneumonia Am. J. Respir. Cell Mol. Biol., June 1, 2008; 38(6): 699 - 706. [Abstract] [Full Text] [PDF] T. Akagi, T. Saitoh, J. O'Kelly, S. Akira, A. F. Gombart, and H. P. Koeffler Impaired response to GM-CSF and G-CSF, and enhanced apoptosis in C/EBP{beta}-deficient hematopoietic cells Blood, March 15, 2008; 111(6): 2999 - 3004. [Abstract] [Full Text] [PDF] S. Kennedy Norton, B. Barnstein, J. Brenzovich, D. P. Bailey, M. Kashyap, K. Speiran, J. Ford, D. Conrad, S. Watowich, M. R. Moralle, et al. IL-10 Suppresses Mast Cell IgE Receptor Expression and Signaling In Vitro and In Vivo J. Immunol., March 1, 2008; 180(5): 2848 - 2854. [Abstract] [Full Text] [PDF] S. M. Holland, F. R. DeLeo, H. Z. Elloumi, A. P. Hsu, G. Uzel, N. Brodsky, A. F. Freeman, A. Demidowich, J. Davis, M. L. Turner, et al. STAT3 Mutations in the Hyper-IgE Syndrome N. Engl. J. Med., October 18, 2007; 357(16): 1608 - 1619. [Abstract] [Full Text] [PDF] M. S. Redell, A. Tsimelzon, S. G. Hilsenbeck, and D. J. Tweardy Conditional overexpression of Stat3{alpha} in differentiating myeloid cells results in neutrophil expansion and induces a distinct, antiapoptotic and pro-oncogenic gene expression pattern J. Leukoc. Biol., October 1, 2007; 82(4): 975 - 985. [Abstract] [Full Text] [PDF] B. T. Kile, A. D. Panopoulos, R. A. Stirzaker, D. F. Hacking, L. H. Tahtamouni, T. A. Willson, L. A. Mielke, K. J. Henley, J.-G. Zhang, I. P. Wicks, et al. Mutations in the cofilin partner Aip1/Wdr1 cause autoinflammatory disease and macrothrombocytopenia Blood, October 1, 2007; 110(7): 2371 - 2380. [Abstract] [Full Text] [PDF] A. C. Hirbe, O. Uluckan, E. A. Morgan, M. C. Eagleton, J. L. Prior, D. Piwnica-Worms, K. Trinkaus, A. Apicelli, and K. Weilbaecher Granulocyte colony-stimulating factor enhances bone tumor growth in mice in an osteoclast-dependent manner Blood, April 15, 2007; 109(8): 3424 - 3431. [Abstract] [Full Text] [PDF] X. O. Yang, A. D. Panopoulos, R. Nurieva, S. H. Chang, D. Wang, S. S. Watowich, and C. Dong STAT3 Regulates Cytokine-mediated Generation of Inflammatory Helper T Cells J. Biol. Chem., March 30, 2007; 282(13): 9358 - 9363. [Abstract] [Full Text] [PDF] P. J. Murray The JAK-STAT Signaling Pathway: Input and Output Integration J. Immunol., March 1, 2007; 178(5): 2623 - 2629. [Abstract] [Full Text] [PDF]

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