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This Article Full Text Full Text (PDF) 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 Maianski, N. A. Articles by Kuijpers, T. W. Search for Related Content PubMed PubMed Citation Articles by Maianski, N. A. Articles by Kuijpers, T. W. Related Collections Phagocytes Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 January 2002, Vol. 99, No. 2, pp. 672-679 PHAGOCYTES Granulocyte colony-stimulating factor inhibits the mitochondria-dependent activation of caspase-3 in neutrophils Nikolai A. Maianski, Frederik P. J. Mul, Jaap D. van Buul, Dirk Roos, and Taco W. Kuijpers From Emma Children's Hospital, Academic Medical Center, University of Amsterdam; Central Laboratory of the Netherlands Blood Transfusion Service (CLB) and Laboratory for Experimental and Clinical Immunology, Academic Medical Center, University of Amsterdam, The Netherlands; Medical Academy, Nizhnyi Novgorod, Russia. The exact mechanism of apoptosis in neutrophils (PMNs) and the explanation for the antiapoptotic effect of granulocyte colony-stimulating factor (G-CSF) in PMNs are unclear. Using specific fluorescent mitochondrial staining, immunofluorescent confocal microscopy, Western blotting, and flow cytometry, this study found that PMNs possess an unexpectedly large number of mitochondria, which are involved in apoptosis. Spontaneous PMN apoptosis was associated with translocation of the Bcl-2-like protein Bax to the mitochondria and subsequent caspase-3 activation, but not with changes in the expression of Bax. G-CSF delayed PMN apoptosis and prevented both associated events. These G-CSF effects were inhibited by cycloheximide. The general caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (zVAD-fmk) prevented caspase-3 activation and apoptosis in PMNs, but not Bax redistribution. PMN-derived cytoplasts, which lack a nucleus, granules, and mitochondria, spontaneously underwent caspase-3 activation and apoptosis (phosphatidylserine exposure), without Bax redistribution. zVAD-fmk inhibited both caspase-3 activation and phosphatidylserine exposure in cultured cytoplasts. Yet, G-CSF prevented neither caspase-3 activation nor apoptosis in cytoplasts, confirming the need for protein synthesis in the G-CSF effects. These data demonstrate that (at least) 2 routes regulate PMN apoptosis: one via Bax-to-mitochondria translocation and a second mitochondria-independent pathway, both linked to caspase-3 activation. Moreover, G-CSF exerts its antiapoptotic effect in the first, that is, mitochondria-dependent, route and has no impact on the second. © 2002 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: A. Drewniak, B. J. van Raam, J. Geissler, A. T.J. Tool, O. R.F. Mook, T. K. van den Berg, F. Baas, and T. W. Kuijpers Changes in gene expression of granulocytes during in vivo granulocyte colony-stimulating factor/dexamethasone mobilization for transfusion purposes Blood, June 4, 2009; 113(23): 5979 - 5998. [Abstract] [Full Text] [PDF] S. A. Didichenko, N. Spiegl, T. Brunner, and C. A. Dahinden IL-3 induces a Pim1-dependent antiapoptotic pathway in primary human basophils Blood, November 15, 2008; 112(10): 3949 - 3958. [Abstract] [Full Text] [PDF] D. El Kebir, L. Jozsef, and J. G. 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