Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF, 1242K) PPT slides of all figures Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Walmsley, S. R. Articles by Chilvers, E. R. Search for Related Content PubMed PubMed Citation Articles by Walmsley, S. R. Articles by Chilvers, E. R. Pubmed/NCBI databases Gene GEO DataSet GEO Profiles HomoloGene UniGene Compound via MeSH Substance via MeSH Related Collections Related Article Social Bookmarking                      What's this?

Hypoxia-induced neutrophil survival is mediated by HIF-1–dependent NF-B activity

¹ Division of Respiratory Medicine, Department of Medicine, School of Clinical Medicine, University of Cambridge, Addenbrooke's and Papworth Hospitals, Cambridge, CB2 2QQ, UK
² Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK
³ Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093

CORRESPONDENCE Edwin Chilvers: erc24{at}hermes.cam.ac.uk

Neutrophils are key effector cells of the innate immune response and are required to migrate and function within adverse microenvironmental conditions. These inflammatory sites are characterized by low levels of oxygen and glucose and high levels of reductive metabolites. A major regulator of neutrophil functional longevity is the ability of these cells to undergo apoptosis. We examined the mechanism by which hypoxia causes an inhibition of neutrophil apoptosis in human and murine neutrophils. We show that neutrophils possess the hypoxia-inducible factor (HIF)-1 and factor inhibiting HIF (FIH) hydroxylase oxygen-sensing pathway and using HIF-1–deficient myeloid cells demonstrate that HIF-1 is directly involved in regulating neutrophil survival in hypoxia. Gene array, TaqMan PCR, Western blotting, and oligonucleotide binding assays identify NF-B as a novel hypoxia-regulated and HIF-dependent target, with inhibition of NF-B by gliotoxin or parthenolide resulting in the abrogation of hypoxic survival. In addition, we identify macrophage inflammatory protein-1ß as a novel hypoxia-induced neutrophil survival factor.

Abbreviations used: DFO, desferrioxamine; DMOG, dimethyloxaloylglycine; FIH, factor inhibiting HIF; GP3DH, glyceraldehyde 3-phosphate dehydrogenase; HIF, hypoxia- inducible factor; IKK, IB kinase-; IB, inhibitor of B; MIF, macrophage migration inhibitory factor; MIP-1ß, macrophage inflammatory protein-1ß; PI3-kinase, phosphoinositide 3-kinase.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

Related Article

Surviving low oxygen

Heather L. Van Epps
J. Exp. Med. 2005 201: 3. [Full Text] [PDF]

This article has been cited by other articles:

• Elia, A. R., Cappello, P., Puppo, M., Fraone, T., Vanni, C., Eva, A., Musso, T., Novelli, F., Varesio, L., Giovarelli, M. (2008). Human dendritic cells differentiated in hypoxia down-modulate antigen uptake and change their chemokine expression profile. J. Leukoc. Biol. 84: 1472-1482 [Abstract] [Full Text]  
• Cowburn, A. S., Condliffe, A. M., Farahi, N., Summers, C., Chilvers, E. R. (2008). Advances in Neutrophil Biology: Clinical Implications. Chest 134: 606-612 [Abstract] [Full Text]  
• Taylor, C. T. (2008). Interdependent roles for hypoxia inducible factor and nuclear factor-{kappa}B in hypoxic inflammation. J. Physiol. 586: 4055-4059 [Abstract] [Full Text]  
• Tacchini, L., Gammella, E., De Ponti, C., Recalcati, S., Cairo, G. (2008). Role of HIF-1 and NF-{kappa}B Transcription Factors in the Modulation of Transferrin Receptor by Inflammatory and Anti-inflammatory Signals. J. Biol. Chem. 283: 20674-20686 [Abstract] [Full Text]  
• Ahn, J. K., Koh, E.-M., Cha, H.-S., Lee, Y. S., Kim, J., Bae, E.-K., Ahn, K.-S. (2008). Role of hypoxia-inducible factor-1{alpha} in hypoxia-induced expressions of IL-8, MMP-1 and MMP-3 in rheumatoid fibroblast-like synoviocytes. Rheumatology (Oxford) 47: 834-839 [Abstract] [Full Text]  
• Nehme, A., Edelman, J. (2008). Dexamethasone Inhibits High Glucose-, TNF-{alpha}-, and IL-1{beta}-Induced Secretion of Inflammatory and Angiogenic Mediators from Retinal Microvascular Pericytes. IOVS 49: 2030-2038 [Abstract] [Full Text]  
• Jantsch, J., Chakravortty, D., Turza, N., Prechtel, A. T., Buchholz, B., Gerlach, R. G., Volke, M., Glasner, J., Warnecke, C., Wiesener, M. S., Eckardt, K.-U., Steinkasserer, A., Hensel, M., Willam, C. (2008). Hypoxia and Hypoxia-Inducible Factor-1{alpha} Modulate Lipopolysaccharide-Induced Dendritic Cell Activation and Function. J. Immunol. 180: 4697-4705 [Abstract] [Full Text]  
• Scortegagna, M., Cataisson, C., Martin, R. J., Hicklin, D. J., Schreiber, R. D., Yuspa, S. H., Arbeit, J. M. (2008). HIF-1{alpha} regulates epithelial inflammation by cell autonomous NF{kappa}B activation and paracrine stromal remodeling. Blood 111: 3343-3354 [Abstract] [Full Text]  
• Walmsley, S. R., McGovern, N. N., Whyte, M. K. B., Chilvers, E. R. (2008). The HIF/VHL Pathway: From Oxygen Sensing to Innate Immunity. Am. J. Respir. Cell Mol. Bio. 38: 251-255 [Abstract] [Full Text]  
• Prince, L. R., Bianchi, S. M., Vaughan, K. M., Bewley, M. A., Marriott, H. M., Walmsley, S. R., Taylor, G. W., Buttle, D. J., Sabroe, I., Dockrell, D. H., Whyte, M. K. B. (2008). Subversion of a Lysosomal Pathway Regulating Neutrophil Apoptosis by a Major Bacterial Toxin, Pyocyanin. J. Immunol. 180: 3502-3511 [Abstract] [Full Text]  
• Dyugovskaya, L., Polyakov, A., Lavie, P., Lavie, L. (2008). Delayed Neutrophil Apoptosis in Patients with Sleep Apnea. Am. J. Respir. Crit. Care Med. 177: 544-554 [Abstract] [Full Text]  
• BelAiba, R. S., Bonello, S., Zahringer, C., Schmidt, S., Hess, J., Kietzmann, T., Gorlach, A. (2007). Hypoxia Up-Regulates Hypoxia-Inducible Factor-1{alpha} Transcription by Involving Phosphatidylinositol 3-Kinase and Nuclear Factor {kappa}B in Pulmonary Artery Smooth Muscle Cells. Mol. Biol. Cell 18: 4691-4697 [Abstract] [Full Text]  
• Hardev Ramandeep Singh Girn, , Ahilathirunayagam, S., Mavor, A. I. D., Homer-Vanniasinkam, S. (2007). Reperfusion Syndrome: Cellular Mechanisms of Microvascular Dysfunction and Potential Therapeutic Strategies. VASC ENDOVASCULAR SURG 41: 277-293 [Abstract]  
• Cooper, D. M., Radom-Aizik, S., Schwindt, C., Zaldivar, F. Jr. (2007). Dangerous exercise: lessons learned from dysregulated inflammatory responses to physical activity. J. Appl. Physiol. 103: 700-709 [Abstract] [Full Text]  
• Levesque, J.-P., Winkler, I. G., Hendy, J., Williams, B., Helwani, F., Barbier, V., Nowlan, B., Nilsson, S. K. (2007). Hematopoietic Progenitor Cell Mobilization Results in Hypoxia with Increased Hypoxia-Inducible Transcription Factor-1{alpha} and Vascular Endothelial Growth Factor A in Bone Marrow. Stem Cells 25: 1954-1965 [Abstract] [Full Text]  
• Peyssonnaux, C., Cejudo-Martin, P., Doedens, A., Zinkernagel, A. S., Johnson, R. S., Nizet, V. (2007). Cutting Edge: Essential Role of Hypoxia Inducible Factor-1{alpha} in Development of Lipopolysaccharide-Induced Sepsis. J. Immunol. 178: 7516-7519 [Abstract] [Full Text]  
• Gombart, A. F., Grewal, J., Koeffler, H. P. (2007). ATF4 differentially regulates transcriptional activation of myeloid-specific genes by C/EBP{epsilon} and C/EBP{alpha}. J. Leukoc. Biol. 81: 1535-1547 [Abstract] [Full Text]  
• Vissers, M. C. M., Wilkie, R. P. (2007). Ascorbate deficiency results in impaired neutrophil apoptosis and clearance and is associated with up-regulation of hypoxia-inducible factor 1{alpha}. J. Leukoc. Biol. 81: 1236-1244 [Abstract] [Full Text]  
• Schuster, D. P., Brody, S. L., Zhou, Z., Bernstein, M., Arch, R., Link, D., Mueckler, M. (2007). Regulation of lipopolysaccharide-induced increases in neutrophil glucose uptake. Am. J. Physiol. Lung Cell. Mol. Physiol. 292: L845-L851 [Abstract] [Full Text]  
• Veschini, L., Belloni, D., Foglieni, C., Cangi, M. G., Ferrarini, M., Caligaris-Cappio, F., Ferrero, E. (2007). Hypoxia-inducible transcription factor-1 alpha determines sensitivity of endothelial cells to the proteosome inhibitor bortezomib. Blood 109: 2565-2570 [Abstract] [Full Text]  
• Viemann, D., Schmidt, M., Tenbrock, K., Schmid, S., Muller, V., Klimmek, K., Ludwig, S., Roth, J., Goebeler, M. (2007). The Contact Allergen Nickel Triggers a Unique Inflammatory and Proangiogenic Gene Expression Pattern via Activation of NF-{kappa}B and Hypoxia-Inducible Factor-1{alpha}. J. Immunol. 178: 3198-3207 [Abstract] [Full Text]  
• Maity, A., Koumenis, C. (2006). HIF and MIF--a nifty way to delay senescence?. Genes Dev. 20: 3337-3341 [Full Text]  
• Walmsley, S. R., Cowburn, A. S., Clatworthy, M. R., Morrell, N. W., Roper, E. C., Singleton, V., Maxwell, P., Whyte, M. K. B., Chilvers, E. R. (2006). Neutrophils from patients with heterozygous germline mutations in the von Hippel Lindau protein (pVHL) display delayed apoptosis and enhanced bacterial phagocytosis. Blood 108: 3176-3178 [Abstract] [Full Text]  
• Asikainen, T. M., Chang, L.-Y., Coalson, J. J., Schneider, B. K., Waleh, N. S., Ikegami, M., Shannon, J. M., Winter, V. T., Grubb, P., Clyman, R. I., Yoder, B. A., Crapo, J. D., White, C. W. (2006). Improved lung growth and function through hypoxia-inducible factor in primate chronic lung disease of prematurity. FASEB J. 20: 1698-1700 [Abstract] [Full Text]  
• Lu, H., Ouyang, W., Huang, C. (2006). Inflammation, a Key Event in Cancer Development. Mol Cancer Res 4: 221-233 [Abstract] [Full Text]  
• Maxwell, P. H (2005). Hypoxia-inducible factor as a physiological regulator. Exp Physiol 90: 791-797 [Abstract] [Full Text]  
• Walmsley, S. R., Print, C., Farahi, N., Peyssonnaux, C., Johnson, R. S., Cramer, T., Sobolewski, A., Condliffe, A. M., Cowburn, A. S., Johnson, N., Chilvers, E. R. (2005). Hypoxia-induced neutrophil survival is mediated by HIF-1{alpha}-dependent NF-{kappa}B activity. JCB 168: i3-i3 [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS