Siglec-8 - A novel eosinophil-specific member of the immunoglobulin superfamily

The Wellcome Trust Biocentre at Dundee, Department of Biochemistry, University of Dundee, Dundee DD1 5EH, Scotland, United Kingdom.
Journal of Biological Chemistry (Impact Factor: 4.57). 02/2000; 275(2):861-6. DOI: 10.1074/jbc.275.2.861
Source: PubMed


We describe the characterization of siglec-8, a novel sialic acid-binding immunoglobulin-like lectin that is expressed specifically by eosinophils. A full-length cDNA encoding siglec-8 was isolated from a human eosinophil cDNA library. Siglec-8 is predicted to contain three extracellular immunoglobulin-like domains, a transmembrane region, and a cytoplasmic tail of 47 amino acids. The siglec-8 gene mapped on chromosome 19q13.33-41, closely linked to genes encoding CD33 (siglec-3), siglec-5, siglec-6, and siglec-7. When siglec-8 was expressed on COS cells or as a recombinant protein fused to the Fc region of human IgG(1), it was able to mediate sialic acid-dependent binding to human erythrocytes and to soluble sialoglycoconjugates. Using specific monoclonal antibodies, siglec-8 could be detected only on eosinophils and hence appears to be the first example of an eosinophil-specific transmembrane receptor.

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    • "Siglec-3/CD33 related-siglecs express mostly on haematopoetic cell lineages. Siglec-9 is expressed on neutrophils, monocytes, fraction of natural killer (NK) cells, B cells etc., while siglec-8 appearance is restricted on the circulating eosinophils and negligible on besophils141516. Several siglecs can be present on the same cells, such as monocytes express siglec-3, -5, -7, -9 and -10 indicating the extent of functional redundancy at cellular level17181920. "
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    ABSTRACT: Sialic acids (Sias) are nine-carbon keto sugars primarily present on the terminal residue of cell surface glycans. Sialic acid binding immunoglobulins (Ig)-like lectins (siglecs) are generally expressed on various immune cells. They selectively recognize different linkage-specific sialic acids and undertake a variety of cellular functions. Many pathogens either synthesize or acquire sialic acids from the host. Sialylated pathogens generally use siglecs to manipulate the host immune response. The present review mainly deals with the newly developed information regarding mechanism of acquisition of sialic acids by pathogens and their biological relevance especially in the establishment of successful infection by impairing host innate immunity. The pathogens which are unable to synthesize sialic acids might adsorb these from the host as a way to engage the inhibitory siglecs. They promote association with the immune cells through sialic acids-siglec dependent manner. Such an association plays an important role to subvert host's immunity. Detailed investigation of these pathways has been discussed in this review. Particular attention has been focused on Pseudomonas aeruginosa (PA) and Leishmania donovani.
    The Indian Journal of Medical Research 11/2013; 138(5):648-62. · 1.40 Impact Factor
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    • "Sn/CD169 is a member of the siglec receptor family whose members are widely expressed on immune cells of man and mouse, including neutrophils, eosinophils, basophils, monocytes, B cells, NK cells, macrophages and dendritic cells [7], [8], [26]–[28]. The restricted expression patterns of siglecs on different cell types and their roles as regulators of immune cell functions, have made them attractive targets for developing cell-directed therapies [9]. "
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    ABSTRACT: Sialoadhesin (Sn, Siglec-1, CD169) is a member of the sialic acid binding Ig-like lectin (siglec) family expressed on macrophages. Its macrophage specific expression makes it an attractive target for delivering antigens to tissue macrophages via Sn-mediated endocytosis. Here we describe a novel approach for delivering antigens to macrophages using liposomal nanoparticles displaying high affinity glycan ligands of Sn. The Sn-targeted liposomes selectively bind to and are internalized by Sn-expressing cells, and accumulate intracellularly over time. Our results show that ligand decorated liposomes are specific for Sn, since they are taken up by bone marrow derived macrophages that are derived from wild type but not Sn(-/-) mice. Importantly, the Sn-targeted liposomes dramatically enhance the delivery of antigens to macrophages for presentation to and proliferation of antigen-specific T cells. Together, these data provide insights into the potential of cell-specific targeting and delivery of antigens to intracellular organelles of macrophages using Sn-ligand decorated liposomal nanoparticles.
    PLoS ONE 06/2012; 7(6):e39039. DOI:10.1371/journal.pone.0039039 · 3.23 Impact Factor
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    • "Eosinophils express a restricted profile of Siglecs [2-5]. Of the eight mouse Siglecs and fourteen human Siglecs that have been identified, eosinophils are reported to highly express significant levels of Siglec-F in mice [2-5] and its functionally convergent ortholog Siglec-8 in human eosinophils [6-8]. Most of the CD33rSiglecs are expressed on cells involved in innate immunity, such as monocytes, granulocytes, macrophages and natural killer cells [1]. "
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    ABSTRACT: In this study we examined the role of Siglec-F, a receptor highly expressed on eosinophils, in contributing to mucus expression, airway remodeling, and Siglec-F ligand expression utilizing Siglec-F deficient mice exposed to chronic allergen challenge. Wild type (WT) and Siglec-F deficient mice were sensitized and challenged chronically with OVA for one month. Levels of airway inflammation (eosinophils), Siglec-F ligand expresion and remodeling (mucus, fibrosis, smooth muscle thickness, extracellular matrix protein deposition) were assessed in lung sections by image analysis and immunohistology. Airway hyperreactivity to methacholine was assessed in intubated and ventilated mice. Siglec-F deficient mice challenged with OVA for one month had significantly increased numbers of BAL and peribronchial eosinophils compared to WT mice which was associated with a significant increase in mucus expression as assessed by the number of periodic acid Schiff positive airway epithelial cells. In addition, OVA challenged Siglec-F deficient mice had significantly increased levels of peribronchial fibrosis (total lung collagen, area of peribronchial trichrome staining), as well as increased numbers of peribronchial TGF-β1+ cells, and increased levels of expression of the extracellular matrix protein fibronectin compared to OVA challenged WT mice. Lung sections immunostained with a Siglec-Fc to detect Siglec-F ligand expression demonstrated higher levels of expression of the Siglec-F ligand in the peribronchial region in OVA challenged Siglec-F deficient mice compared to WT mice. WT and Siglec-F deficient mice challenged intranasally with IL-4 or IL-13 had significantly increased levels of airway epithelial Siglec-F ligand expression, whereas this was not observed in WT or Siglec-F deficient mice challenged with TNF-α. There was a significant increase in the thickness of the peribronchial smooth muscle layer in OVA challenged Siglec-F deficient mice, but this was not associated with significant increased airway hyperreactivity compared to WT mice. Overall, this study demonstrates an important role for Siglec-F in modulating levels of chronic eosinophilic airway inflammation, peribronchial fibrosis, thickness of the smooth muscle layer, mucus expression, fibronectin, and levels of peribronchial Siglec-F ligands suggesting that Siglec-F may normally function to limit levels of chronic eosinophilic inflammation and remodeling. In addition, IL-4 and IL-13 are important regulators of Siglec-F ligand expression by airway epithelium.
    Respiratory research 11/2010; 11(1):154. DOI:10.1186/1465-9921-11-154 · 3.09 Impact Factor
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