Siglec-8. A novel eosinophil-specific member of the immunoglobulin superfamily.
ABSTRACT 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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ABSTRACT: Siglec-F and Siglec-8 are functional paralog proapoptotic cell surface receptors expressed on mouse and human eosinophils, respectively. Whereas Siglec-8 mediated death involves caspases and/or reactive oxygen species (ROS) generation and mitochondrial injury, very little is known about Siglec-F-mediated signaling and apoptosis. Therefore the objective of the current experiments was to better define apoptosis pathways mediated by Siglec-F and Siglec-8. Given that Siglec-F-induced apoptosis is much less robust than Siglec-8-induced apoptosis, we hypothesized that mechanisms involved in cell death via these receptors would differ. Consequences of engagement of Siglec-F on mouse eosinophils were studied by measuring ROS production, and by performing apoptosis assays using eosinophils from normal, hypereosinophilic, NADPH oxidase-deficient, src homology domain-containing protein tyrosine phosphatase (SHP)-1-deficient, and Lyn kinase-deficient mice. Inhibitors of caspase and Src family kinase activity were also used. Engagement of Siglec-F induced mouse eosinophil apoptosis that was modest in magnitude and dependent on caspase activity. There was no detectable ROS generation, or any role for ROS, NADPH oxidase, SHP-1, or Src family kinases in this apoptotic process. These data suggest that Siglec-F-mediated apoptosis is different in both magnitude and mechanisms when compared to published data on Siglec-8-mediated human eosinophil apoptosis. One likely implication of this work is that models targeting Siglec-F in vivo in mice may not provide identical mechanistic predictions for consequences of Siglec-8 targeting in vivo in humans.PLoS ONE 01/2013; 8(6):e68143. · 3.53 Impact Factor
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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. · 2.06 Impact Factor