SEARCH:   Advanced

Prepublished online as a Blood First Edition Paper on May 13, 2002; DOI 10.1182/blood-2001-11-0122. This Article Full Text (PDF) All Versions of this Article: 2001-11-0122v1 100/7/2607    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 Cowburn, A. S Articles by Chilvers, E. R Search for Related Content PubMed PubMed Citation Articles by Cowburn, A. S Articles by Chilvers, E. R Social Bookmarking                   What's this? Submitted December 3, 2001 Accepted April 27, 2002 Role of PI3-kinase-dependent Bad phosphorylation and altered transcription in cytokine-mediated neutrophil survival Andrew S Cowburn, Karen A Cadwallader, Benjamin J Reed, Neda Farahi, and Edwin R Chilvers* Respiratory Medicine Division, Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Cambridge, Cambridgeshire, United Kingdom * Corresponding author; email: erc24{at}hermes.cam.ac.uk. Phosphoinositide 3-kinase (PI3-kinase) dependent phosphorylation of the pro-apoptotic Bcl-2 family member Bad has been proposed as an important regulator of apoptotic cell death. To understand the importance of this pathway in non-transformed haematopoietic cells we have examined the effect of survival cytokines on PI3-kinase activity and Bad expression and phosphorylation status in human neutrophils. GM-CSF and TNF both reduced the rate of apoptosis in neutrophils cultured in vitro for 20 hrs. Co-incubation with the PI3-kinase inhibitor LY294002, which in parallel experiments abolished GM-CSF primed, fMLP-stimulated superoxide anion production and GM-CSF-stimulated PtdIns(3,4,5)P3 accumulation, inhibited the GM-CSF and TNF survival effect. In contrast, the MEK1/2 inhibitor PD98059 and the PKA inhibitor H-89 had only a marginal effect on GM-CSF-mediated neutrophil survival. GM-CSF substantially increased Bad phosphorylation at ser-112 and ser-136 and increased the cytosolic accumulation of Bad. GM-CSF also regulated Bad at a transcription level with a marked decrease in mRNA levels at 4 hrs. TNF caused a biphasic effect on the rate of morphological apoptosis, which corresponded to an early increase, and late inhibition, of Bad mRNA levels. LY294002 inhibited both GM-CSF and TNF-mediated changes in Bad phosphorylation and mRNA levels. These data suggest that the survival effect of GM-CSF and TNF in neutrophils is caused by a PI3-kinase-dependent phosphorylation and cytosolic translocation of Bad together with an inhibition of Bad mRNA levels. This has important implications for the regulation of neutrophil apoptosis in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Himpe, C. Degaillier, A. Coppens, and R. Kooijman Insulin-like growth factor-1 delays Fas-mediated apoptosis in human neutrophils through the phosphatidylinositol-3 kinase pathway J. Endocrinol., October 1, 2008; 199(1): 69 - 80. [Abstract] [Full Text] [PDF] C. A. Fielding, R. M. McLoughlin, L. McLeod, C. S. Colmont, M. Najdovska, D. Grail, M. Ernst, S. A. Jones, N. Topley, and B. J. Jenkins IL-6 Regulates Neutrophil Trafficking during Acute Inflammation via STAT3 J. Immunol., August 1, 2008; 181(3): 2189 - 2195. [Abstract] [Full Text] [PDF] K. Omori, T. Ohira, Y. Uchida, S. Ayilavarapu, E. L. Batista Jr., M. Yagi, T. Iwata, H. Liu, H. Hasturk, A. Kantarci, et al. Priming of neutrophil oxidative burst in diabetes requires preassembly of the NADPH oxidase J. Leukoc. Biol., July 1, 2008; 84(1): 292 - 301. [Abstract] [Full Text] [PDF] N. Farahi, A. S. Cowburn, P. D. Upton, J. Deighton, A. Sobolewski, E. Gherardi, N. W. Morrell, and E. R. Chilvers Eotaxin-1/CC Chemokine Ligand 11: A Novel Eosinophil Survival Factor Secreted by Human Pulmonary Artery Endothelial Cells J. Immunol., July 15, 2007; 179(2): 1264 - 1273. [Abstract] [Full Text] [PDF] G. Seumois, M. Fillet, L. Gillet, C. Faccinetto, C. Desmet, C. Francois, B. Dewals, C. Oury, A. Vanderplasschen, P. Lekeux, et al. De novo C16- and C24-ceramide generation contributes to spontaneous neutrophil apoptosis J. Leukoc. Biol., June 1, 2007; 81(6): 1477 - 1486. [Abstract] [Full Text] [PDF] C. Tortorella, O. Simone, G. Piazzolla, I. Stella, V. Cappiello, and S. Antonaci Role of Phosphoinositide 3-Kinase and Extracellular Signal-Regulated Kinase Pathways in Granulocyte Macrophage-Colony-Stimulating Factor Failure to Delay Fas-Induced Neutrophil Apoptosis in Elderly Humans J. Gerontol. A Biol. Sci. Med. Sci., November 1, 2006; 61(11): 1111 - 1118. [Abstract] [Full Text] [PDF] S. R. Walmsley, A. S. Cowburn, M. R. Clatworthy, N. W. Morrell, E. C. Roper, V. Singleton, P. Maxwell, M. K. B. Whyte, and E. R. Chilvers Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis Blood, November 1, 2006; 108(9): 3176 - 3178. [Abstract] [Full Text] [PDF] N. Omidvar, L. Pearn, A. K. Burnett, and R. L. Darley Ral Is both Necessary and Sufficient for the Inhibition of Myeloid Differentiation Mediated by Ras Mol. Cell. Biol., May 15, 2006; 26(10): 3966 - 3975. [Abstract] [Full Text] [PDF] A. S. Cowburn, A. Sobolewski, B. J. Reed, J. Deighton, J. Murray, K. A. Cadwallader, J. R. Bradley, and E. R. Chilvers Aminopeptidase N (CD13) Regulates Tumor Necrosis Factor-{alpha}-induced Apoptosis in Human Neutrophils J. Biol. Chem., May 5, 2006; 281(18): 12458 - 12467. [Abstract] [Full Text] [PDF] C. A. Lindemans, P. J. Coffer, I. M. M. Schellens, P. M. A. de Graaff, J. L. L. Kimpen, and L. Koenderman Respiratory Syncytial Virus Inhibits Granulocyte Apoptosis through a Phosphatidylinositol 3-Kinase and NF-{kappa}B-Dependent Mechanism J. Immunol., May 1, 2006; 176(9): 5529 - 5537. [Abstract] [Full Text] [PDF] S. D. Kobayashi, J. M. Voyich, A. R. Whitney, and F. R. DeLeo Spontaneous neutrophil apoptosis and regulation of cell survival by granulocyte macrophage-colony stimulating factor J. Leukoc. Biol., December 1, 2005; 78(6): 1408 - 1418. [Abstract] [Full Text] [PDF] A V Kamath, I D Pavord, P R Ruparelia, and E R Chilvers Is the neutrophil the key effector cell in severe asthma? Thorax, July 1, 2005; 60(7): 529 - 530. [Full Text] [PDF] A. Bruno, S. Conus, I. Schmid, and H.-U. Simon Apoptotic Pathways Are Inhibited by Leptin Receptor Activation in Neutrophils J. Immunol., June 15, 2005; 174(12): 8090 - 8096. [Abstract] [Full Text] [PDF] L. C. Parker, M. K. B. Whyte, S. K. Dower, and I. Sabroe The expression and roles of Toll-like receptors in the biology of the human neutrophil J. Leukoc. Biol., June 1, 2005; 77(6): 886 - 892. [Abstract] [Full Text] [PDF] V. Pinho, D. G. Souza, M. M. Barsante, F. P. Hamer, M. S. De Freitas, A. G. Rossi, and M. M. Teixeira Phosphoinositide-3 kinases critically regulate the recruitment and survival of eosinophils in vivo: importance for the resolution of allergic inflammation J. Leukoc. Biol., May 1, 2005; 77(5): 800 - 810. [Abstract] [Full Text] [PDF] Z. Hu and M. M. Sayeed Activation of PI3-kinase/PKB contributes to delay in neutrophil apoptosis after thermal injury Am J Physiol Cell Physiol, May 1, 2005; 288(5): C1171 - C1178. [Abstract] [Full Text] [PDF] A. S. Cowburn, J. F. White, J. Deighton, S. R. Walmsley, and E. R. Chilvers z-VAD-fmk augmentation of TNF{alpha}-stimulated neutrophil apoptosis is compound specific and does not involve the generation of reactive oxygen species Blood, April 1, 2005; 105(7): 2970 - 2972. [Abstract] [Full Text] [PDF] S. Francois, J. El Benna, P. M. C. Dang, E. Pedruzzi, M.-A. Gougerot-Pocidalo, and C. Elbim Inhibition of Neutrophil Apoptosis by TLR Agonists in Whole Blood: Involvement of the Phosphoinositide 3-Kinase/Akt and NF-{kappa}B Signaling Pathways, Leading to Increased Levels of Mcl-1, A1, and Phosphorylated Bad J. Immunol., March 15, 2005; 174(6): 3633 - 3642. [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] Y. Kotone-Miyahara, K. Yamashita, K.-K. Lee, S. Yonehara, T. Uchiyama, M. Sasada, and A. Takahashi Short-term delay of Fas-stimulated apoptosis by GM-CSF as a result of temporary suppression of FADD recruitment in neutrophils: evidence implicating phosphatidylinositol 3-kinase and MEK1-ERK1/2 pathways downstream of classical protein kinase C J. Leukoc. Biol., November 1, 2004; 76(5): 1047 - 1056. [Abstract] [Full Text] [PDF] L. E. Kilpatrick, S. Sun, and H. M. Korchak Selective regulation by {delta}-PKC and PI 3-kinase in the assembly of the antiapoptotic TNFR-1 signaling complex in neutrophils Am J Physiol Cell Physiol, September 1, 2004; 287(3): C633 - C642. [Abstract] [Full Text] [PDF] R. I. Fernando and J. Wimalasena Estradiol Abrogates Apoptosis in Breast Cancer Cells through Inactivation of BAD: Ras-dependent Nongenomic Pathways Requiring Signaling through ERK and Akt Mol. Biol. Cell, July 1, 2004; 15(7): 3266 - 3284. [Abstract] [Full Text] [PDF] M. Derouet, L. Thomas, A. Cross, R. J. Moots, and S. W. Edwards Granulocyte Macrophage Colony-stimulating Factor Signaling and Proteasome Inhibition Delay Neutrophil Apoptosis by Increasing the Stability of Mcl-1 J. Biol. Chem., June 25, 2004; 279(26): 26915 - 26921. [Abstract] [Full Text] [PDF] R. Boxio, C. Bossenmeyer-Pourie, N. Steinckwich, C. Dournon, and O. Nusse Mouse bone marrow contains large numbers of functionally competent neutrophils J. Leukoc. Biol., April 1, 2004; 75(4): 604 - 611. [Abstract] [Full Text] [PDF] M. Choi, S. Rolle, M. Wellner, M. C. Cardoso, C. Scheidereit, F. C. Luft, and R. Kettritz Inhibition of NF-{kappa}B by a TAT-NEMO-binding domain peptide accelerates constitutive apoptosis and abrogates LPS-delayed neutrophil apoptosis Blood, September 15, 2003; 102(6): 2259 - 2267. [Abstract] [Full Text] [PDF] I. Sabroe, L. R. Prince, E. C. Jones, M. J. Horsburgh, S. J. Foster, S. N. Vogel, S. K. Dower, and M. K. B. Whyte Selective Roles for Toll-Like Receptor (TLR)2 and TLR4 in the Regulation of Neutrophil Activation and Life Span J. Immunol., May 15, 2003; 170(10): 5268 - 5275. [Abstract] [Full Text] [PDF]

	Copyright © 2002 by American Society of Hematology         Online ISSN: 1528-0020