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Blood, 15 April 2008, Vol. 111, No. 8, pp. 3978-3985. Prepublished online as a Blood First Edition Paper on December 21, 2007; DOI 10.1182/blood-2007-10-119636. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-10-119636v1 111/8/3978    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 Walker, F. Articles by Burgess, A. W Search for Related Content PubMed PubMed Citation Articles by Walker, F. Articles by Burgess, A. W Related Collections Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted October 29, 2007 Accepted December 17, 2007 IL6/sIL6R complex contributes to emergency granulopoietic response in G-CSF and GM-CSF deficient mice Francesca Walker*, Hui-Hua Zhang, Vance Matthews, Janet Weinstock, Edouard C Nice, Matthias Ernst, Stefan Rose-John, and Antony W Burgess Ludwig Institute for Cancer Research, Melbournce Tumor Biology Branch, Melbourne, Victoria, Australia JDRF Diabetes & Metabolism Division, Baker Heart Research Institute, Melbourne, Victoria, Australia Biochemisches Institute, Christian-Albrechts-Universitat, Kiel, Germany * Corresponding author; email: francesca.walker{at}ludwig.edu.au. Mice defective in both G-CSF and GM-CSF have severely impaired neutrophil production and function, yet these mice respond to acute pathogen challenge with a significant neutrophil response. We have recently reported the development of an in vitro system to detect granulopoietic cytokines secreted from cells isolated from G-CSF, GM-CSF double knockout mice. The conditioned media (CM) produced by these cells after stimulation with LPS or C.albicans supports the production and differentiation of granulocytes, i.e. the CM contains neutrophil promoting activity (NPA). We now show that the NPA in the G-CSF-/-/GM-CSF-/- conditioned media requires IL-6 , is abolished by soluble gp130, and can be specifically immunodepleted by an anti-IL6R antibody. NPA effects on bone marrow cells are also mimicked by Hyper-IL6, and the soluble IL-6 R is present in NPA. These results show that the IL6/sIL6R complex is the major effector of NPA. NPA production by mice defective for both G-CSF and GM-CSF uncovers an alternative pathway to granulocyte production, which is activated following exposure to pathogens. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: IL6 to the rescue Peter E. Newburger Blood 2008 111: 3914-3915. [Full Text] [PDF] This article has been cited by other articles: Y. Ueda, D. W. Cain, M. Kuraoka, M. Kondo, and G. Kelsoe IL-1R Type I-Dependent Hemopoietic Stem Cell Proliferation Is Necessary for Inflammatory Granulopoiesis and Reactive Neutrophilia J. Immunol., May 15, 2009; 182(10): 6477 - 6484. [Abstract] [Full Text] [PDF] K. Maeda, A. Malykhin, B. N. Teague-Weber, X.-H. Sun, A. D. Farris, and K. M. Coggeshall Interleukin-6 aborts lymphopoiesis and elevates production of myeloid cells in systemic lupus erythematosus-prone B6.Sle1.Yaa animals Blood, May 7, 2009; 113(19): 4534 - 4540. [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]

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