SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on November 14, 2002; DOI 10.1182/blood-2002-07-2132. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-07-2132v1 101/6/2393    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 Villunger, A. Articles by Strasser, A. Search for Related Content PubMed PubMed Citation Articles by Villunger, A. Articles by Strasser, A. Related Collections Phagocytes Apoptosis Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 March 2003, Vol. 101, No. 6, pp. 2393-2400 PHAGOCYTES Essential role for the BH3-only protein Bim but redundant roles for Bax, Bcl-2, and Bcl-w in the control of granulocyte survival Andreas Villunger, Clare Scott, Philippe Bouillet, and Andreas Strasser From the Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia. Programmed cell death of granulocytes is one of the mechanisms that limit inflammatory responses. Members of the Bcl-2 protein family are essential regulators of apoptosis induced by growth factor withdrawal or cytotoxic stress. We have used gene-targeted and transgenic mice to investigate the roles of the prosurvival molecules Bcl-2 and Bcl-w and their proapoptotic relatives Bax and Bim in spontaneous and stress-induced apoptosis of granulocytes from bone marrow or the peritoneum. Bim deficiency, like Bcl-2 overexpression, rendered granulocytes resistant to cytokine withdrawal and cytotoxic drugs, but absence of Bax alone had no protective effect. Loss of Bcl-2 or Bcl-w did not increase the sensitivity of granulocytes to any of these apoptotic stimuli, but Bcl-2 was essential for the in vitro survival of myeloid progenitors under conditions of cytokine withdrawal where cell death was mediated, in part, by Bim. Granulocyte colony-stimulating factor (G-CSF), a key survival factor for granulocytes, enhanced viability of cells lacking bcl-2, bcl-w, bax, or bim, indicating that none of these genes alone is the essential target of this cytokine's prosurvival function. Expression analysis of proapoptotic Bcl-2 family members in granulocytes revealed that the BH3-only protein Bmf is induced upon cytokine withdrawal. These results indicate that the BH3-only protein Bim and possibly also Bmf are critical initiators of spontaneous and drug-induced apoptosis of granulocytes, whereas Bcl-2, Bcl-w, and Bax act in a redundant manner in regulating granulocyte survival and death, respectively. © 2003 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. C. Reed Bcl-2-family proteins and hematologic malignancies: history and future prospects Blood, April 1, 2008; 111(7): 3322 - 3330. [Abstract] [Full Text] [PDF] M. Ekoff, T. Kaufmann, M. Engstrom, N. Motoyama, A. Villunger, J.-I. Jonsson, A. Strasser, and G. Nilsson The BH3-only protein Puma plays an essential role in cytokine deprivation induced apoptosis of mast cells Blood, November 1, 2007; 110(9): 3209 - 3217. [Abstract] [Full Text] [PDF] L. Coultas, S. Terzano, T. Thomas, A. Voss, K. Reid, E. G. Stanley, C. L. Scott, P. Bouillet, P. Bartlett, J. Ham, et al. Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis J. Cell Sci., June 15, 2007; 120(12): 2044 - 2052. [Abstract] [Full Text] [PDF] M. Ekoff, A. Strasser, and G. Nilsson Fc{epsilon}RI Aggregation Promotes Survival of Connective Tissue-Like Mast Cells but Not Mucosal-Like Mast Cells J. Immunol., April 1, 2007; 178(7): 4177 - 4183. [Abstract] [Full Text] [PDF] I. Dzhagalov, A. St. John, and Y.-W. He The antiapoptotic protein Mcl-1 is essential for the survival of neutrophils but not macrophages Blood, February 15, 2007; 109(4): 1620 - 1626. [Abstract] [Full Text] [PDF] J. Pierce, J. Rir-Sima-Ah, I. Estrada, J. Wilder, A. Strasser, and Y. Tesfaigzi Loss of pro-apoptotic Bim promotes accumulation of pulmonary T lymphocytes and enhances allergen-induced goblet cell metaplasia Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L862 - L870. [Abstract] [Full Text] [PDF] P. G. Ekert, A. M. Jabbour, A. Manoharan, J. E. Heraud, J. Yu, M. Pakusch, E. M. Michalak, P. N. Kelly, B. Callus, T. Kiefer, et al. Cell death provoked by loss of interleukin-3 signaling is independent of Bad, Bim, and PI3 kinase, but depends in part on Puma Blood, September 1, 2006; 108(5): 1461 - 1468. [Abstract] [Full Text] [PDF] M. Erlacher, E. M. Michalak, P. N. Kelly, V. Labi, H. Niederegger, L. Coultas, J. M. Adams, A. Strasser, and A. Villunger BH3-only proteins Puma and Bim are rate-limiting for {gamma}-radiation- and glucocorticoid-induced apoptosis of lymphoid cells in vivo Blood, December 15, 2005; 106(13): 4131 - 4138. [Abstract] [Full Text] [PDF] C. Clybouw, B. Mchichi, S. Mouhamad, M. T. Auffredou, M. F. Bourgeade, S. Sharma, G. Leca, and A. Vazquez EBV Infection of Human B Lymphocytes Leads to Down-Regulation of Bim Expression: Relationship to Resistance to Apoptosis J. Immunol., September 1, 2005; 175(5): 2968 - 2973. [Abstract] [Full Text] [PDF] C. Moller, J. Alfredsson, M. Engstrom, H. Wootz, Z. Xiang, J. Lennartsson, J.-I. Jonsson, and G. Nilsson Stem cell factor promotes mast cell survival via inactivation of FOXO3a-mediated transcriptional induction and MEK-regulated phosphorylation of the proapoptotic protein Bim Blood, August 15, 2005; 106(4): 1330 - 1336. [Abstract] [Full Text] [PDF] J. Hutcheson, J. C. Scatizzi, E. Bickel, N. J. Brown, P. Bouillet, A. Strasser, and H. Perlman Combined loss of proapoptotic genes Bak or Bax with Bim synergizes to cause defects in hematopoiesis and in thymocyte apoptosis J. Exp. Med., June 20, 2005; 201(12): 1949 - 1960. [Abstract] [Full Text] [PDF] S. R. Walmsley, C. Print, N. Farahi, C. Peyssonnaux, R. S. Johnson, T. Cramer, A. Sobolewski, A. M. Condliffe, A. S. Cowburn, N. Johnson, et al. Hypoxia-induced neutrophil survival is mediated by HIF-1{alpha}-dependent NF-{kappa}B activity J. Exp. Med., January 3, 2005; 201(1): 105 - 115. [Abstract] [Full Text] [PDF] W. D. Cook, B. J. McCaw, C. Herring, D. L. John, S. J. Foote, S. L. Nutt, and J. M. Adams PU.1 is a suppressor of myeloid leukemia, inactivated in mice by gene deletion and mutation of its DNA binding domain Blood, December 1, 2004; 104(12): 3437 - 3444. [Abstract] [Full Text] [PDF] M. Pellegrini, P. Bouillet, M. Robati, G. T. Belz, G. M. Davey, and A. Strasser Loss of Bim Increases T Cell Production and Function in Interleukin 7 Receptor-deficient Mice J. Exp. Med., November 1, 2004; 200(9): 1189 - 1195. [Abstract] [Full Text] [PDF] S. Okuno, A. Saito, T. Hayashi, and P. H. Chan The c-Jun N-Terminal Protein Kinase Signaling Pathway Mediates Bax Activation and Subsequent Neuronal Apoptosis through Interaction with Bim after Transient Focal Cerebral Ischemia J. Neurosci., September 8, 2004; 24(36): 7879 - 7887. [Abstract] [Full Text] [PDF] K. E. Lawlor, I. K. Campbell, D. Metcalf, K. O'Donnell, A. van Nieuwenhuijze, A. W. Roberts, and I. P. Wicks Critical role for granulocyte colony-stimulating factor in inflammatory arthritis PNAS, August 3, 2004; 101(31): 11398 - 11403. [Abstract] [Full Text] [PDF]

	Copyright © 2003 by American Society of Hematology         Online ISSN: 1528-0020