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Blood, 15 May 2007, Vol. 109, No. 10, pp. 4280-4287. Prepublished online as a Blood First Edition Paper on February 1, 2007; DOI 10.1182/blood-2006-08-039255. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figures All Versions of this Article: blood-2006-08-039255v1 109/10/4280    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 Zhang, M. Articles by Varki, A. Search for Related Content PubMed PubMed Citation Articles by Zhang, M. Articles by Varki, A. Related Collections Immunobiology Phagocytes Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Defining the in vivo function of Siglec-F, a CD33-related Siglec expressed on mouse eosinophils Mai Zhang1, Takashi Angata1, Jae Youn Cho1, Marina Miller1, David H. Broide1, and Ajit Varki1 1 Glycobiology Research and Training Center, Departments of Medicine and Cellular & Molecular Medicine, and Biomedical Sciences Graduate Program, University of California at San Diego, CA CD33-related Siglecs (CD33rSiglecs) are a family of sialic acid–recognizing lectins on immune cells whose biologic functions are unknown. We studied in vivo functions of Siglec-F, the CD33rSiglec expressed on mouse eosinophils, which are prominent in allergic processes. Induction of allergic lung inflammation in mice caused up-regulation of Siglec-F on blood and bone marrow eosinophils, accompanied by newly induced expression on some CD4+ cells, as well as quantitative up-regulation of endogenous Siglec-F ligands in the lung tissue and airways. Taken together with the tyrosine-based inhibitory motif in the cytosolic tail of Siglec-F, the data suggested a negative feedback loop, controlling allergic responses of eosinophils and helper T cells, via Siglec-F and Siglec-F ligands. To pursue this hypothesis, we created Siglec-F–null mice. Allergen-challenged null mice showed increased lung eosinophil infiltration, enhanced bone marrow and blood eosinophilia, delayed resolution of lung eosinophilia, and reduced peribronchial-cell apoptosis. Anti–Siglec-F antibody cross-linking also enhanced eosinophil apoptosis in vitro. These data support the proposed negative feedback role for Siglec-F, represent the first in vivo demonstration of biologic functions for any CD33rSiglec, and predict a role for human Siglec-8 (the isofunctional paralog of mouse Siglec-F) in regulating the pathogenesis of human eosinophil-mediated disorders. 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. Varki Natural ligands for CD33-related Siglecs? Glycobiology, August 1, 2009; 19(8): 810 - 812. [Full Text] [PDF] A. C. Kirby, M. C. Coles, and P. M. Kaye Alveolar Macrophages Transport Pathogens to Lung Draining Lymph Nodes J. Immunol., August 1, 2009; 183(3): 1983 - 1989. [Abstract] [Full Text] [PDF] D. H. Lim, J. Y. Cho, D. J. Song, S. Y. Lee, M. Miller, and D. H. Broide PI3K{gamma}-deficient mice have reduced levels of allergen-induced eosinophilic inflammation and airway remodeling Am J Physiol Lung Cell Mol Physiol, February 1, 2009; 296(2): L210 - L219. [Abstract] [Full Text] [PDF] T. A. Doherty, P. Soroosh, D. H. Broide, and M. Croft CD4+ cells are required for chronic eosinophilic lung inflammation but not airway remodeling Am J Physiol Lung Cell Mol Physiol, February 1, 2009; 296(2): L229 - L235. [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] H. Tateno, H. Li, M. J. Schur, N. Bovin, P. R. Crocker, W. W. Wakarchuk, and J. C. Paulson Distinct Endocytic Mechanisms of CD22 (Siglec-2) and Siglec-F Reflect Roles in Cell Signaling and Innate Immunity Mol. Cell. Biol., August 15, 2007; 27(16): 5699 - 5710. [Abstract] [Full Text] [PDF]

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