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Blood, 15 November 2008, Vol. 112, No. 10, pp. 3949-3958. Prepublished online as a Blood First Edition Paper on September 2, 2008; DOI 10.1182/blood-2008-04-149419. This Article Full Text Full Text (PDF) Supplemental Methods and Figures All Versions of this Article: blood-2008-04-149419v1 112/10/3949    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 Didichenko, S. A. Articles by Dahinden, C. A. Search for Related Content PubMed PubMed Citation Articles by Didichenko, S. A. Articles by Dahinden, C. A. Related Collections Immunobiology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils Svetlana A. Didichenko1, Nicole Spiegl1, Thomas Brunner2, and Clemens A. Dahinden1 1 Institute of Immunology and 2 Institute of Pathology, University of Bern, Bern, Switzerland The contribution of basophils in allergic disease and other Th2-type immune responses depends on their persistence at sites of inflammation, but the ligands and molecular pathways supporting basophil survival are largely unknown. The comparison of rates of apoptosis and of the expression of antiapoptotic proteins in different human granulocyte types revealed that basophils have a considerably longer spontaneous life span than neutrophils and eosinophils consistent with high levels of constitutive Bcl-2 expression. Interleukin-3 (IL-3) is the only ligand that efficiently protects basophils from apoptosis as evidenced by screening a large number of stimuli. IL-3 up-regulates the expression of the antiapoptotic proteins cIAP2, Mcl-1, and Bcl-XL and induces a rapid and sustained de novo expression of the serine/threonine kinase Pim1 that closely correlates with cytokine-enhanced survival. Inhibitor studies and protein transduction of primary basophils using wild-type and kinase-dead Pim1-Tat fusion-proteins demonstrate the functional importance of Pim1 induction in the IL-3–enhanced survival. Our data further indicate that the antiapoptotic Pim1-mediated pathway operates independently of PI3-kinase but involves the activation of p38 MAPK. The induction of Pim1 leading to PI3-kinase–independent survival as described here for basophils may also be a relevant antiapoptotic mechanism in other terminally differentiated leukocyte types. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: M. F. Gurish The expanding universe of the basophil Blood, March 19, 2009; 113(12): 2616 - 2616. [Full Text] [PDF] T. Pecaric-Petkovic, S. A. Didichenko, S. Kaempfer, N. Spiegl, and C. A. Dahinden Human basophils and eosinophils are the direct target leukocytes of the novel IL-1 family member IL-33 Blood, February 12, 2009; 113(7): 1526 - 1534. [Abstract] [Full Text] [PDF]

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