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Blood, 15 January 2005, Vol. 105, No. 2, pp. 592-599. Prepublished online as a Blood First Edition Paper on September 14, 2004; DOI 10.1182/blood-2004-07-2838. This Article Full Text (PDF) All Versions of this Article: 2004-07-2838v1 105/2/592    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 Kulka, M. Articles by Metcalfe, D. D Search for Related Content PubMed PubMed Citation Articles by Kulka, M. Articles by Metcalfe, D. D Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 23, 2004 Accepted August 23, 2004 High resolution tracking of cell division demonstrates differential effects of Th1 and Th2 cytokines on SCF-dependent human mast cell production in vitro: correlation with apoptosis and Kit expression Marianna Kulka and Dean D Metcalfe* Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA * Corresponding author; email: dmetcalfe{at}niaid.nih.gov. Th1 (IFN-) and Th2 (IL-4 and IL-5) cytokines have been variably reported to alter human mast cell (HuMC) numbers in complex culture systems. The effects of these cytokines on the kinetics of cell division and cell death are unknown and their effect on MC behavior is relevant to anticipate the consequences of in vivo strategies that alter cytokine levels. To determine the effect of these cytokines on SCF-dependent HuMC production, we used high resolution tracking of cell division and correlated the results with cell apoptosis, expression of Kit, and on mast cell degranulation. When IFN-, IL-5 or IL-4 were administered over 8 weeks, we found each cytokine decreased MC number through a different mechanism. IFN- inhibited early progenitor cell division, IL-4 downregulated early Kit expression and IL-5 blocked later cell division. Further, IL-4 and IFN- had the greatest suppressive effect on degranulation and FcRI expression. When these cytokines were administered to mature mast cells, IFN- and IL-5 had no affect on degranulation and cell division, but IL-4 induced division and potentiated FcRI-mediated degranulation. Thus, exposure of HuMC to IL-4, IL-5 and IFN- during growth and differentiation, generally downregulated MC number and function, while IL-4 increased mature MC division and degranulation. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: N. M. Kushnir-Sukhov, A. M. Gilfillan, J. W. Coleman, J. M. Brown, S. Bruening, M. Toth, and D. D. Metcalfe 5-Hydroxytryptamine Induces Mast Cell Adhesion and Migration J. Immunol., November 1, 2006; 177(9): 6422 - 6432. [Abstract] [Full Text] [PDF] Y. Jiang, Y. Kanaoka, C. Feng, K. Nocka, S. Rao, and J. A. Boyce Cutting edge: interleukin 4-dependent mast cell proliferation requires autocrine/intracrine cysteinyl leukotriene-induced signaling. J. Immunol., September 1, 2006; 177(5): 2755 - 2759. [Abstract] [Full Text] [PDF] M. N. Mann-Chandler, M. Kashyap, H. V. Wright, F. Norozian, B. O. Barnstein, S. Gingras, E. Parganas, and J. J. Ryan IFN-{gamma} Induces Apoptosis in Developing Mast Cells J. Immunol., September 1, 2005; 175(5): 3000 - 3005. [Abstract] [Full Text] [PDF]

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