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Prepublished online as a Blood First Edition Paper on June 28, 2002; DOI 10.1182/blood-2002-02-0454. This Article Full Text (PDF) All Versions of this Article: 2002-02-0454v1 100/8/3008    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 Mecklenburgh, K. I Articles by Chilvers, E. R Search for Related Content PubMed PubMed Citation Articles by Mecklenburgh, K. I Articles by Chilvers, E. R Social Bookmarking                   What's this? Submitted February 12, 2002 Accepted June 6, 2002 Involvement of a ferro-protein sensor in hypoxia-mediated inhibition of neutrophil apoptosis Katy I Mecklenburgh, Sarah R Walmsley, Andrew S Cowburn, Michael Wiesener, Benjamin J Reed, Paul D Upton, John Deighton, Andrew P Greening, and Edwin R Chilvers* Department of Medicine, University of Edinburgh, Edinburgh, Scotland, United Kingdom Department of Medicine, University of Cambridge, Cambridge, Cambridgeshire, United Kingdom Wellcome Trust Centre for Human Genetics, Institute of Molecular Medicine, Oxford, Oxfordshire, United Kingdom Respiratory Medicine, Western General Hospital, Edinburgh, Scotland, United Kingdom * Corresponding author; email: erc24{at}hermes.cam.ac.uk. Neutrophil apoptosis represents a major mechanism involved in the resolution of acute inflammation. In contrast to the effect of hypoxia observed in many other cell types we have shown that oxygen deprivation causes a profound but reversible delay in the rate of constitutive apoptosis in human neutrophils when aged in vitro. This effect was mimicked by exposing cells to two structurally unrelated iron-chelating agents, desferrioxamine (DFO) and hydroxypyridones (CP-94), and appeared specific for hypoxia in that no modulation of apoptosis was observed with mitochondrial electron transport inhibitors, glucose deprivation or heat shock. The involvement of chelatable iron in the oxygen sensing mechanism was confirmed by the abolition of the DFO and CP-94 survival effect by Fe2+ ions. While HIF-1 mRNA was identified in freshly isolated neutrophils, HIF-1 protein was only detected in neutrophils incubated under hypoxic conditions or in the presence of DFO. Moreover, studies with cyclohexamide demonstrated that the survival effect of hypoxia was fully dependent on continuing protein synthesis. These results indicate that the neutrophil has an identical ferro-protein oxygen sensing mechanism to that identified for erythropoietin regulation and results in both HIF-1 upregulation and a profound but reversible inhibition of neutrophil apoptosis. This finding may have important implications for the resolution of granulocytic inflammation at sites of low oxygen tension. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. H. Wong, N. Francis, H. Chahal, K. Raza, M. Salmon, D. Scheel-Toellner, and J. M. Lord Lactoferrin is a survival factor for neutrophils in rheumatoid synovial fluid Rheumatology, January 1, 2009; 48(1): 39 - 44. [Abstract] [Full Text] [PDF] S. R. Walmsley, N. N. McGovern, M. K. B. Whyte, and E. R. 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