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Prepublished online as a Blood First Edition Paper on August 8, 2002; DOI 10.1182/blood-2002-06-1778. This Article Full Text (PDF) All Versions of this Article: 2002-06-1778v1 100/13/4446    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 Sordet, O. Articles by Dubrez-Daloz, L. Search for Related Content PubMed PubMed Citation Articles by Sordet, O. Articles by Dubrez-Daloz, L. Social Bookmarking                   What's this? Submitted June 14, 2002 Accepted July 23, 2002 Specific involvement of caspases in the differentiation of monocytes into macrophages Olivier Sordet, Cedric Rebe, Stephanie Plenchette, Yael Zermati, Olivier Hermine, William Vainchenker, Carmen Garrido, Eric Solary*, and Laurence Dubrez-Daloz IFR100, Faculty of Medicine, INSERM Unite 517, Dijon, France IFR Necker, CNRS UMR 8603, Paris, France Institut Gustave Roussy, INSERM Unite 362, Villejuif, France * Corresponding author; email: esolary{at}u-bourgogne.fr. Caspases are cysteine proteases involved in apoptosis and cytokine maturation. In erythroblasts, keratinocytes and lens epithelial cells undergoing differentiation, enucleation has been regarded as a caspase-mediated incomplete apoptotic process. Here, we show that several caspases are activated in human peripheral blood monocytes whose differentiation into macrophages is induced by M-CSF. This activation is not associated with cell death and cannot be detected in monocytes undergoing dendritic cell differentiation in the presence of IL-4 and GM-CSF. The mechanisms and consequences of caspase activation were further studied in U937 human monocytic cells undergoing phorbol ester-induced differentiation into macrophages. Differentiation-associated caspase activation involves the release of cytochrome c from the mitochondria and leads to the cleavage of the protein acinus while the poly(ADP-ribose)polymerase remains uncleaved. Inhibition of caspases by either exposure to the broad spectrum inhibitor z-VAD-fmk or expression of the p35 baculovirus inhibitory protein or overexpression of Bcl-2 inhibits the differentiation process. In addition, z-VAD-fmk amplifies the differentiation-associated production of radical oxygen species in both phorbol ester-differentiated U937 cells and M-CSF-treated monocytes, shifting the differentiation process to non-apoptotic cell death. Altogether, these results indicate that caspase activation specifically contributes to the differentiation of monocytes into macrophages, in the absence of cell death. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Jacquel, N. Benikhlef, J. Paggetti, N. Lalaoui, L. Guery, E. K. Dufour, M. Ciudad, C. Racoeur, O. Micheau, L. Delva, et al. Colony-stimulating factor-1-induced oscillations in phosphatidylinositol-3 kinase/AKT are required for caspase activation in monocytes undergoing differentiation into macrophages Blood, October 22, 2009; 114(17): 3633 - 3641. [Abstract] [Full Text] [PDF] J.-W. Hsu, H.-C. Huang, S.-T. Chen, C.-H. Wong, and H.-F. Juan Ganoderma lucidum Polysaccharides Induce Macrophage-like Differentiation in Human Leukemia THP-1 Cells via Caspase and p53 Activation Evid. Based Complement. Altern. Med., August 20, 2009; (2009) nep107v1. [Abstract] [Full Text] [PDF] B. Shi, T. Tran, R. 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