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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: A. F. Carlin, S. Uchiyama, Y.-C. Chang, A. L. Lewis, V. Nizet, and A. 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