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Blood, 15 August 2005, Vol. 106, No. 4, pp. 1423-1431. Prepublished online as a Blood First Edition Paper on April 12, 2005; DOI 10.1182/blood-2004-10-4112. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4112v1 106/4/1423    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map 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 von Gunten, S. Articles by Simon, H.-U. Search for Related Content PubMed PubMed Citation Articles by von Gunten, S. Articles by Simon, H.-U. Related Collections Phagocytes Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  PHAGOCYTES Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflammatory cytokine environment Stephan von Gunten, Shida Yousefi, Michael Seitz, Stephan M. Jakob, Thomas Schaffner, Reinhard Seger, Jukka Takala, Peter M. Villiger, and Hans-Uwe Simon From the Department of Pharmacology, the Department of Rheumatology/Clinical Immunology/Allergology, the Department of Intensive Care Medicine, and the Department of Pathology, University Hospital Bern; and University Children's Hospital of Zurich, Switzerland. We report about new apoptotic and non-apoptotic death pathways in neutrophils that are initiated via the surface molecule sialic acid-binding immunoglobulin-like lectin (Siglec)-9. In normal neutrophils, Siglec-9 ligation induced apoptosis. Inflammatory neutrophils obtained from patients with acute septic shock or rheumatoid arthritis demonstrated increased Siglec-9, but normal Fas receptor-mediated cytotoxic responses when compared with normal blood neutrophils. The increased Siglec-9-mediated death was mimicked in vitro by short-term preincubation of normal neutrophils with proinflammatory cytokines, such as granulocyte/macrophage colony-stimulating factor (GM-CSF), interferon- (IFN-), and IFN-, and was demonstrated to be caspase independent. Experiments using scavengers of reactive oxygen species (ROS) or neutrophils unable to generate ROS indicated that both Siglec-9-mediated caspase-dependent and caspase-independent forms of neutrophil death depend on ROS. Interestingly, the caspase-independent form of neutrophil death was characterized by cytoplasmic vacuolization and several other nonapoptotic morphologic features, which were also seen in neutrophils present in joint fluids from rheumatoid arthritis patients. Taken together, these data suggest that apoptotic (ROS- and caspase-dependent) and nonapoptotic (ROS-dependent) death pathways are initiated in neutrophils via Siglec-9. The new insights have important implications for the pathogenesis, diagnosis, and treatment of inflammatory diseases such as sepsis and rheumatoid arthritis. (Blood. 2005;106:1423-1431) CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Song, J. Y. Cho, S. Y. Lee, M. Miller, P. Rosenthal, P. Soroosh, M. Croft, M. Zhang, A. Varki, and D. H. Broide Anti-Siglec-F Antibody Reduces Allergen-Induced Eosinophilic Inflammation and Airway Remodeling J. Immunol., October 15, 2009; 183(8): 5333 - 5341. [Abstract] [Full Text] [PDF] A. Daryadel, S. Yousefi, D. Troi, I. Schmid, J. Schmidt-Mende, C. Mordasini, C. A. Dahinden, A. Ziemiecki, and H.-U. Simon RhoH/TTF Negatively Regulates Leukotriene Production in Neutrophils J. 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[Abstract] [Full Text] [PDF] R. B. Walter, B. W. Raden, R. Zeng, P. Hausermann, I. D. Bernstein, and J. A. Cooper ITIM-dependent endocytosis of CD33-related Siglecs: role of intracellular domain, tyrosine phosphorylation, and the tyrosine phosphatases, Shp1 and Shp2 J. Leukoc. Biol., January 1, 2008; 83(1): 200 - 211. [Abstract] [Full Text] [PDF] I. Can, S. Tahara-Hanaoka, K. Hitomi, T. Nakano, C. Nakahashi-Oda, N. Kurita, S.-i. Honda, K. Shibuya, and A. Shibuya Caspase-Independent Cell Death by CD300LF (MAIR-V), an Inhibitory Immunoglobulin-Like Receptor on Myeloid Cells J. Immunol., January 1, 2008; 180(1): 207 - 213. [Abstract] [Full Text] [PDF] T. Angata, Y. Tabuchi, K. Nakamura, and M. Nakamura Siglec-15: an immune system Siglec conserved throughout vertebrate evolution Glycobiology, August 1, 2007; 17(8): 838 - 846. [Abstract] [Full Text] [PDF] M. Zhang, T. Angata, J. Y. Cho, M. Miller, D. H. Broide, and A. 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Varki, and M. Nakamura Discovery of Siglec-14, a novel sialic acid receptor undergoing concerted evolution with Siglec-5 in primates FASEB J, October 1, 2006; 20(12): 1964 - 1973. [Abstract] [Full Text] [PDF] A. Daryadel, R. F. Grifone, H.-U. Simon, and S. Yousefi Apoptotic Neutrophils Release Macrophage Migration Inhibitory Factor upon Stimulation with Tumor Necrosis Factor-{alpha} J. Biol. Chem., September 15, 2006; 281(37): 27653 - 27661. [Abstract] [Full Text] [PDF] J. Zhang, A. Raper, N. Sugita, R. Hingorani, M. Salio, M. J. Palmowski, V. Cerundolo, and P. R. Crocker Characterization of Siglec-H as a novel endocytic receptor expressed on murine plasmacytoid dendritic cell precursors Blood, May 1, 2006; 107(9): 3600 - 3608. [Abstract] [Full Text] [PDF] S. von Gunten and H.-U. Simon Sialic acid binding immunoglobulin-like lectins may regulate innate immune responses by modulating the life span of granulocytes FASEB J, April 1, 2006; 20(6): 601 - 605. [Abstract] [Full Text] [PDF]

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