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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- "For example, Siglec-5 is myeloid-specific but, unlike CD33, is expressed on neutrophils in addition to monocytes (Cornish et al, 1998; Mason et al, 2002a). Siglec-8 is found only on 'allergic cells' (eosinophils, mast cells and basophils) (Floyd et al, 2000; Kikly et al, 2000), while Siglec-7 is expressed on natural killer (NK) cells, monocytes and dendritic cells (Falco et al, 1999; Nicoll et al, 1999). Siglec-9 and -10 have a more diverse expression as Siglec-9 is present on some NK cells and B cells as well as on neutrophils and monocytes and Siglec- 10 is detected on eosinophils, monocytes, dendritic cells and a minor population of NK cells (Zhang et al, 2000; Li et al, 2001; Munday et al, 2001). "
ABSTRACT: Sialic acid-binding immunoglobulin-like lectin (Siglec)-5 or CD170 is a CD33-related receptor, containing cytoplasmic immune receptor-based tyrosine signalling motifs, that has previously been reported to be myeloid-specific like CD33 and thus may be useful in the characterization of both normal and malignant haemopoiesis. This study showed that Siglec-5 had a distinct expression pattern to CD33 both on normal myeloid cells and in acute myeloid leukaemia (AML). In normal bone marrow and cord blood, myeloid cells predominantly expressed Siglec-5 at the later stages of granulocytic differentiation. Siglec-5 was not expressed at significant levels by CD34+ progenitors either from bone marrow or mobilized peripheral blood. During in vitro myeloid differentiation of cord blood purified CD34+ cells, Siglec-5 was upregulated later than CD33. Siglec-5 expression remained absent or very low on cultured CD34+ cells, unlike CD33, which was present on almost all CD34+ cells by day 4. However, analysis of blasts from 23 patients with AML revealed aberrant expression of Siglec-5 with CD34 in 50% (seven of 14) of patients with CD34+ AML; 61% (14 of 23) of AML cases were positive for Siglec-5 with an increased frequency in the French-American-British subtypes M3-5 (80%) compared with M0-2 (25%). All 13 acute lymphoblastic leukaemic (ALL) samples tested, including a CD33+ ALL, were Siglec-5 negative. These results support the further evaluation of Siglec-5 antibodies in the diagnosis and monitoring of AML.British Journal of Haematology 12/2003; 123(3):420-30. DOI:10.1046/j.1365-2141.2003.04625.x · 4.96 Impact Factor
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- "Previous studies have shown indistinguishable ligand binding by both mouse and human sialoadhesins (Hartnell et al., 2001). CHO cells stably secreting chimeric proteins comprising the extracellular regions of siglec proteins fused to the Fc portion of human IgG1 were prepared as described previously (Crocker et al., 1994; Cornish et al., 1998; Nicoll et al., 1999; Floyd et al., 2000; Zhang et al., 2000; Munday et al., 2001). All contained the entire extracellular region of each siglec with the exception of mouse and human Sn, which had the first three and four N-terminal Ig domains respectively. "
ABSTRACT: Sialic acid-binding immunoglobulin-like lectins (siglecs) are expressed predominantly in the haemopoietic and immune systems and exhibit specificities for both the linkage and the nature of sialic acids in N-glycans, O-glycans and glycolipids. Several siglecs, including sialoadhesin (Sn, siglec-1) and siglec-5, bind to NeuAcalpha2,3Gal, a terminal capping structure that can also be displayed on the lipopolysaccharide (LPS) of Neisseria meningitidis (Nm). In the present study, we examined the potential of siglecs expressed on cells of the immune system to function as receptors for sialylated Nm. We used sialylated and non-sialylated LPS derivatives of two serogroups (A and B) of Nm in this study. Using recombinant chimeric soluble receptors, siglec-transfected cell lines and macrophages from wild-type and Sn-deficient mice, we observed that sialylated but not non-sialylated variants of either genetic background were specifically recognized by Sn and siglec-5, whereas other siglecs examined were ineffective. In addition, macrophages expressing Sn, as well as transfectants expressing Sn or siglec-5, bound and phagocytosed sialylated bacteria in a siglec- and sialic acid-dependent manner. This study demonstrates that Nm LPS sialylation can lead to increased bacterial susceptibility to phagocytic uptake, a phenomenon in direct contrast to previously reported protective effects of LPS sialylation.Molecular Microbiology 10/2003; 49(5):1213-25. DOI:10.1046/j.1365-2958.2003.03634.x · 5.03 Impact Factor
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- "as shown by the binding to sialidase-treated wild-type B lymphocytes but not to sialidase-treated lymphocytes from CD22-null mice. This is a key finding because five different Siglecs have been reported on human B cells, and the overlapping sialoside specificity of the Siglecs with probes studied to date is well documented (Angata et al., 2001; Angata and Varki, 2000a; Cornish et al., 1998; Floyd et al., 2000a,b; Munday et al., 2001; Nicoll et al., 1999; Patel et al., 1999; Yu et al., 2001; Zhang et al., 2000). Thus, these probes are anticipated to be useful tools in future investigations of the function of the carbohydrate ligand in modulating the role of CD22 in B cell signaling in the murine model. "
ABSTRACT: The interaction of CD22 with glycoprotein ligands bearing the Siaalpha2,6Gal-R sequence is believed to modulate its function as a regulator of B cell signaling. Although a commercial sialoside-polyacrylamide (PAA) probe, NeuAc- alpha2,6Gal-PAA, has facilitated studies on ligand binding by human CD22, murine CD22 binds instead with high affinity to NeuGcalpha2,6Gal-R. A multivalent probe with this sequence was constructed to facilitate investigations of ligand binding in CD22 function using genetically defined murine models. The probe is based on the sialoside-PAA platform, which is then biotinylated for easy detection. A series of sialoside probes were constructed with two different length linker arms between the sialoside and the backbone and three different sialoside to PAA molar ratios. The NeuGcalpha2,6Gal-PAA probe is specific for CD22: it binds to sialidase-treated B cells of wild-type mice but not B cells of CD22-null mice. Additionally, because the probe only binds to sialidase-treated wild-type cells, it confirms that CD22 is constitutively "masked" on most B cells from wild-type mice by binding to ligands in cis. In contrast, the probe bound equally well to native or sialidase-treated B cells from the immunocompromised ligand-deficient ST6Gal I knockout mice, demonstrating that CD22 is constitutively "unmasked" in these cells.Glycobiology 10/2002; 12(9):563-71. DOI:10.1093/glycob/cwf067 · 3.75 Impact Factor