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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3209-3217. Prepublished online as a Blood First Edition Paper on July 18, 2007; DOI 10.1182/blood-2007-02-073957. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-02-073957v1 110/9/3209    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Ekoff, M. Articles by Nilsson, G. Search for Related Content PubMed PubMed Citation Articles by Ekoff, M. Articles by Nilsson, G. Related Collections Apoptosis Chemokines, Cytokines, and Interleukins Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY The BH3-only protein Puma plays an essential role in cytokine deprivation–induced apoptosis of mast cells Maria Ekoff1, Thomas Kaufmann2, Maria Engström3, Noboru Motoyama4, Andreas Villunger5, Jan-Ingvar Jönsson3, Andreas Strasser2, and Gunnar Nilsson1 1 Department of Medicine, Clinical Immunology and Allergy Unit, Karolinska Institutet, Stockholm, Sweden; 2 Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; 3 Division of Cell Biology, Department of Biomedicine and Surgery, Linköping University, Linköping, Sweden, 4 Department of Geriatric Medicine, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, Obu, Japan; and 5 Division of Developmental Immunology, Biocenter, Innsbruck Medical University, Innsbruck, Austria Mast cells play critical roles in the regulation of inflammation. One characteristic feature of mast cells is their relatively long lifespan in vivo. Members of the Bcl-2 protein family are regulators of cell survival and apoptosis, where the BH3-only proteins are critical proapoptotic proteins. In this study we investigated the role of the BH3-only proteins Noxa, Bad, Bim, Bmf, Bid, and Puma in apoptosis of mucosal-like mast cells (MLMCs) and connective tissue–like mast cells (CTLMCs). We demonstrate that Puma is critical for the induction of mast-cell death following cytokine deprivation and treatment with the DNA-damaging agent etoposide in MLMCs and CTLMCs. Using p53–/– mast cells, we found that cytokine deprivation–induced apoptosis, in contrast to that elicited by etoposide, is p53-independent. Interestingly, mast cells deficient in FOXO3a, previously proposed as a transcription factor for Puma induction in response to growth factor deprivation, were markedly resistant to cytokine withdrawal compared with wild-type cells. Moreover, overexpression of phosphorylation-deficient, constitutively active FOXO3a caused an up-regulation of Puma. In conclusion, our data demonstrate a pivotal role for Puma in the regulation of cytokine deprivation–induced mast-cell apoptosis and suggest a plausible role for Puma in the regulation of mast cell numbers in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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