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Blood, 15 January 2008, Vol. 111, No. 2, pp. 878-884. Prepublished online as a Blood First Edition Paper on October 17, 2007; DOI 10.1182/blood-2007-05-087833. This Article Full Text (PDF) All Versions of this Article: blood-2007-05-087833v1 111/2/878    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 Cross, A. Articles by Edwards, S. W Search for Related Content PubMed PubMed Citation Articles by Cross, A. Articles by Edwards, S. W Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted May 30, 2007 Accepted September 9, 2007 The dual effects of TNF on neutrophil apoptosis are mediated via differential effects on expression of Mcl-1 and Bfl-1 Andrew Cross, Robert J Moots, and Steven W Edwards* School of Biological Sciences, University of Liverpool, Liverpool, United Kingdom School of Clinical Sciences, University of Liverpool, Liverpool, United Kingdom * Corresponding author; email: s.w.edwards{at}liv.ac.uk. Neutrophils have a very short half life in the circulation, undergoing rapid death by apoptosis, but a number of agents can either delay or accelerate the rate at which these cells undergo death. TNF can exert opposing, concentration-dependent effects on neutrophils to either accelerate their apoptosis or enhance their survival. We show that TNF greatly increases the rate of turnover of Mcl-1, an anti-apoptotic protein that plays a key role in neutrophil survival. In contrast to Mcl-1 turnover in control or GM-CSF treated neutrophils that occurs via the proteasome, TNF accelerated Mcl-1 turnover occurs via activation of caspases. Mcl-1 depleted cells thus have accelerated rates of apoptosis. While TNF had no effect on MCL-1 transcription, it induced expression of another anti-apoptotic molecule, Bfl-1. Low concentrations of TNF ( 1 ng/mL) stimulated BFL-1 expression whereas higher concentrations ( 10 ng/mL) triggered caspase-dependent acceleration of Mcl-1 turnover. These opposing effects on two separate anti-apoptotic systems of neutrophils explains the divergent effects of TNF on neutrophil apoptosis and has important implications for understanding how TNF may affect immune function in inflammatory diseases. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. Paunel-Gorgulu, M. Zornig, T. Logters, J. Altrichter, U. Rabenhorst, J. Cinatl, J. Windolf, and M. Scholz Mcl-1-Mediated Impairment of the Intrinsic Apoptosis Pathway in Circulating Neutrophils from Critically Ill Patients Can Be Overcome by Fas Stimulation J. Immunol., November 15, 2009; 183(10): 6198 - 6206. [Abstract] [Full Text] [PDF] S. Moriceau, C. Kantari, J. Mocek, N. Davezac, J. Gabillet, I. C. Guerrera, F. Brouillard, D. Tondelier, I. Sermet-Gaudelus, C. Danel, et al. Coronin-1 Is Associated with Neutrophil Survival and Is Cleaved during Apoptosis: Potential Implication in Neutrophils from Cystic Fibrosis Patients J. Immunol., June 1, 2009; 182(11): 7254 - 7263. [Abstract] [Full Text] [PDF] D. M. Pritchard, D. Berry, S. M. C. Przemeck, F. Campbell, S. W. Edwards, and A. Varro Gastrin increases mcl-1 expression in type I gastric carcinoid tumors and a gastric epithelial cell line that expresses the CCK-2 receptor Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G798 - G805. [Abstract] [Full Text] [PDF] M. Hurtado-Nedelec, S. Chollet-Martin, P. Nicaise-Roland, S. Grootenboer-Mignot, R. Ruimy, O. Meyer, and G. Hayem Characterization of the immune response in the synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome Rheumatology, August 1, 2008; 47(8): 1160 - 1167. [Abstract] [Full Text] [PDF]

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