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Prepublished online as a Blood First Edition Paper on February 27, 2003; DOI 10.1182/blood-2002-10-3058. This Article Full Text Full Text (PDF) All Versions of this Article: 2002-10-3058v1 101/12/5014    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 Nutku, E. Articles by Bochner, B. S. Search for Related Content PubMed PubMed Citation Articles by Nutku, E. Articles by Bochner, B. S. Related Collections Phagocytes Apoptosis Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 15 June 2003, Vol. 101, No. 12, pp. 5014-5020 PHAGOCYTES Ligation of Siglec-8: a selective mechanism for induction of human eosinophil apoptosis Esra Nutku, Hideyuki Aizawa, Sherry A. Hudson, and Bruce S. Bochner From the Johns Hopkins Asthma and Allergy Center, Johns Hopkins University School of Medicine, Baltimore, MD. Sialic acid binding immunoglobulin-like lectin 8 (Siglec-8), which exists in 2 isoforms including one possessing cytoplasmic tyrosine motifs, is expressed only on human eosinophils, basophils, and mast cells. Until now, its function was unknown. Here we define a novel function of Siglec-8 on eosinophils. Siglec-8 cross-linking with antibodies rapidly generated caspase-3–like activity and reduced eosinophil viability through induction of apoptosis. The pancaspase inhibitor benzyloxycarbonyl (Cbz)–Val-Ala-Asp-(Ome)-fluoromethyl ketone (zVAD-FMK) completely blocked this response, implicating caspases in Siglec-8 cross-linking–induced apoptosis. Eosinophil survival-promoting cytokines such as interleukin 5 (IL-5) and granulocyte-macrophage colony-stimulating factor (GM-CSF) failed to block apoptosis and instead enhanced the sensitivity of eosinophils to undergo apoptosis in response to Siglec-8 antibody. Siglec-8 activation may provide a useful therapeutic approach to reduce numbers of eosinophils (and perhaps basophils and mast cells) in disease states where these cells are important. 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] S. A. Hudson, N. V. Bovin, R. L. Schnaar, P. R. Crocker, and B. S. Bochner Eosinophil-Selective Binding and Proapoptotic Effect in Vitro of a Synthetic Siglec-8 Ligand, Polymeric 6'-Sulfated Sialyl Lewis X J. Pharmacol. Exp. Ther., August 1, 2009; 330(2): 608 - 612. [Abstract] [Full Text] [PDF] A. F. Carlin, S. Uchiyama, Y.-C. Chang, A. L. Lewis, V. Nizet, and A. Varki Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response Blood, April 2, 2009; 113(14): 3333 - 3336. [Abstract] [Full Text] [PDF] A. Munitz, M. L. McBride, J. S. Bernstein, and M. E. Rothenberg A dual activation and inhibition role for the paired immunoglobulin-like receptor B in eosinophils Blood, June 15, 2008; 111(12): 5694 - 5703. [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] E. Nutku-Bilir, S. A. Hudson, and B. S. Bochner Interleukin-5 Priming of Human Eosinophils Alters Siglec-8 Mediated Apoptosis Pathways Am. J. Respir. Cell Mol. Biol., January 1, 2008; 38(1): 121 - 124. [Abstract] [Full Text] [PDF] J. Yoon, A. Terada, and H. Kita CD66b Regulates Adhesion and Activation of Human Eosinophils J. Immunol., December 15, 2007; 179(12): 8454 - 8462. [Abstract] [Full Text] [PDF] C. Ohnmacht, A. Pullner, N. van Rooijen, and D. Voehringer Analysis of Eosinophil Turnover In Vivo Reveals Their Active Recruitment to and Prolonged Survival in the Peritoneal Cavity J. Immunol., October 1, 2007; 179(7): 4766 - 4774. [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. Varki Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils Blood, May 15, 2007; 109(10): 4280 - 4287. [Abstract] [Full Text] [PDF] S. J. Orr, N. M. Morgan, R. J. Buick, C. R. Boyd, J. Elliott, J. F. Burrows, C. A. Jefferies, P. R. Crocker, and J. A. Johnston SOCS3 Targets Siglec 7 for Proteasomal Degradation and Blocks Siglec 7-mediated Responses J. Biol. Chem., February 9, 2007; 282(6): 3418 - 3422. [Abstract] [Full Text] [PDF] S. J. Orr, N. M. Morgan, J. Elliott, J. F. Burrows, C. J. Scott, D. W. McVicar, and J. A. Johnston CD33 responses are blocked by SOCS3 through accelerated proteasomal-mediated turnover Blood, February 1, 2007; 109(3): 1061 - 1068. [Abstract] [Full Text] [PDF] T. Angata, T. Hayakawa, M. Yamanaka, A. 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. Munitz, I. Bachelet, R. Eliashar, M. Khodoun, F. D. Finkelman, M. E. Rothenberg, and F. Levi-Schaffer CD48 Is an Allergen and IL-3-Induced Activation Molecule on Eosinophils J. Immunol., July 1, 2006; 177(1): 77 - 83. [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] A. Munitz, I. Bachelet, R. Eliashar, A. Moretta, L. Moretta, and F. Levi-Schaffer The inhibitory receptor IRp60 (CD300a) suppresses the effects of IL-5, GM-CSF, and eotaxin on human peripheral blood eosinophils Blood, March 1, 2006; 107(5): 1996 - 2003. [Abstract] [Full Text] [PDF] E. Lopez, V. del Pozo, T. Miguel, B. Sastre, C. Seoane, E. Civantos, E. Llanes, M. L. Baeza, P. Palomino, B. Cardaba, et al. Inhibition of Chronic Airway Inflammation and Remodeling by Galectin-3 Gene Therapy in a Murine Model J. Immunol., February 1, 2006; 176(3): 1943 - 1950. [Abstract] [Full Text] [PDF] A. Varki and T. Angata Siglecs--the major subfamily of I-type lectins Glycobiology, January 1, 2006; 16(1): 1R - 27R. [Abstract] [Full Text] [PDF] I. Bachelet, A. Munitz, A. Moretta, L. Moretta, and F. Levi-Schaffer The Inhibitory Receptor IRp60 (CD300a) Is Expressed and Functional on Human Mast Cells J. Immunol., December 15, 2005; 175(12): 7989 - 7995. [Abstract] [Full Text] [PDF] H. Tateno, P. R. Crocker, and J. C. Paulson Mouse Siglec-F and human Siglec-8 are functionally convergent paralogs that are selectively expressed on eosinophils and recognize 6'-sulfo-sialyl Lewis X as a preferred glycan ligand Glycobiology, November 1, 2005; 15(11): 1125 - 1135. [Abstract] [Full Text] [PDF] S. von Gunten, S. Yousefi, M. Seitz, S. M. Jakob, T. Schaffner, R. Seger, J. Takala, P. M. Villiger, and H.-U. Simon Siglec-9 transduces apoptotic and nonapoptotic death signals into neutrophils depending on the proinflammatory cytokine environment Blood, August 15, 2005; 106(4): 1423 - 1431. [Abstract] [Full Text] [PDF] B. S. Bochner, R. A. Alvarez, P. Mehta, N. V. Bovin, O. Blixt, J. R. White, and R. L. Schnaar Glycan Array Screening Reveals a Candidate Ligand for Siglec-8 J. Biol. Chem., February 11, 2005; 280(6): 4307 - 4312. [Abstract] [Full Text] [PDF] A. Munitz, I. Bachelet, S. Fraenkel, G. Katz, O. Mandelboim, H.-U. Simon, L. Moretta, M. Colonna, and F. Levi-Schaffer 2B4 (CD244) Is Expressed and Functional on Human Eosinophils J. Immunol., January 1, 2005; 174(1): 110 - 118. [Abstract] [Full Text] [PDF] Y. Ikehara, S. K. Ikehara, and J. C. Paulson Negative Regulation of T Cell Receptor Signaling by Siglec-7 (p70/AIRM) and Siglec-9 J. Biol. Chem., October 8, 2004; 279(41): 43117 - 43125. [Abstract] [Full Text] [PDF] L. Uller, M. Andersson, L. Greiff, C. G. A. Persson, and J. S. Erjefalt Occurrence of Apoptosis, Secondary Necrosis, and Cytolysis in Eosinophilic Nasal Polyps Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 742 - 747. [Abstract] [Full Text] [PDF] T. Angata, E. H. Margulies, E. D. Green, and A. Varki Large-scale sequencing of the CD33-related Siglec gene cluster in five mammalian species reveals rapid evolution by multiple mechanisms PNAS, September 7, 2004; 101(36): 13251 - 13256. [Abstract] [Full Text] [PDF]

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