SEARCH:   Advanced

Blood, 1 September 2008, Vol. 112, No. 5, pp. 2046-2054. Prepublished online as a Blood First Edition Paper on June 4, 2008; DOI 10.1182/blood-2008-04-149575. This Article Full Text (PDF) All Versions of this Article: blood-2008-04-149575v1 112/5/2046    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 van Raam, B. J Articles by Kuijpers, T. W. Search for Related Content PubMed PubMed Citation Articles by van Raam, B. J Articles by Kuijpers, T. W. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted April 3, 2008 Accepted May 12, 2008 Granulocyte colony-stimulating factor delays neutrophil apoptosis by inhibition of calpains upstream of caspase-3 Bram J van Raam*, Agata Drewniak, Vincent Groenewold, Timo K van den Berg, and Taco W. Kuijpers Blood Cell Research and Phagocyte Laboratory, Sanquin Research and Landsteiner Laboratory, Amsterdam, Netherlands Emma Children's Hospital, Academic Medical Center (AMC), Amsterdam, Netherlands * Corresponding author; email: b.j.vanraam{at}gmail.com. Neutrophils have a very short life span and undergo apoptosis within 24 hours after leaving the bone marrow. Granulocyte colony-stimulating factor (G-CSF) is essential for the recruitment of fresh neutrophils from the bone marrow but also delays apoptosis of mature neutrophils. To determine the mechanism by which G-CSF inhibits neutrophil apoptosis, the kinetics of neutrophil apoptosis during 24 hours in the absence or presence of G-CSF were analyzed in vitro. G-CSF delayed neutrophil apoptosis for about 12 hours and inhibited caspase-9 and -3 activation, but had virtually no effect on caspase-8 and little effect on the release of pro-apoptotic proteins from the mitochondria. However, G-CSF strongly inhibited the activation of calcium-dependent cysteine proteases calpains, upstream of caspase-3, via apparent control of Ca2+-influx. Calpain inhibition resulted in the stabilization of the X-linked inhibitor of apoptosis (XIAP) and hence inhibited caspase-9 and -3 in human neutrophils. Thus, neutrophil apoptosis is controlled by G-CSF after initial activation of caspase-8 and mitochondrial permeabilization by the control of post-mitochondrial calpain activity. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: Y. Yokoyama, T. Suzuki, M. Sakata-Yanagimoto, K. Kumano, K. Higashi, T. Takato, M. Kurokawa, S. Ogawa, and S. Chiba Derivation of functional mature neutrophils from human embryonic stem cells Blood, June 25, 2009; 113(26): 6584 - 6592. [Abstract] [Full Text] [PDF] 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. 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]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020