Disease relevance of Siglec1

• 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) [1].
• Myelin mutants devoid of Sn show reduced numbers of CD8+ T lymphocytes and macrophages in peripheral nerves and less severe demyelination, resulting in improved nerve conduction properties [2].
• The toxicity index defined by 1/LD50/7 was parallel to the sensitizing activity measured by 1/DS,1.5 (DS,1.5 is the sensitizer dose to obtain the SER of 1.5 in vivo) [3].
• In the studies of experimental salmonellosis, immunization of mice with a live vaccine SER of S. enteritidis was found to be effective against further infection with virulent S. enteritidis 116--54 [4].
• Mortalities and weight gains of mice treated with Se were also reduced when Sn was administered simultaneously [5].

High impact information on Siglec1

• Analysis of the complex with 3'sialyllactose highlights three residues, conserved throughout the siglec family, as key features of the sialic acid-binding template [6].
• In this study we present evidence that the mouse and rat sialoadhesin (originally named sheep erythrocyte receptor) on macrophages can function as a lymphocyte adhesion molecule [7].
• An inhibitory rat mAb, SER-4, has been raised to the mouse macrophage (M phi)-restricted hemagglutinin, sheep erythrocyte receptor (SER), which binds unopsonized sheep erythrocytes through recognition of sialylated glycoconjugates [8].
• These results therefore confirm that SER is a novel M phi-restricted receptor whose distribution and properties indicate a role in cellular interactions in hematopoietic and lymphoid tissues [8].
• The inhibition was likely to be via steric hindrance rather than through a direct interaction with the putative sialic acid binding site of SER because F(ab')2 and Fab fragments of mAb SER-4 gave a maximum inhibition of 50-60% and 0% respectively, despite binding effectively to the SER-4 antigen (Ag) [8].

Biological context of Siglec1

• Extended glycoconjugate binding specificities of three sialic acid-dependent immunoglobulin-like family member lectins (siglecs), myelin-associated glycoprotein (MAG), Schwann cell myelin protein (SMP), and sialoadhesin, were compared by measuring siglec-mediated cell adhesion to immobilized gangliosides [9].
• In the present study, we investigated the pathogenetic impact of CD11b+ macrophages by crossbreeding the myelin mutants with knockout mice deficient for the macrophage-restricted adhesion molecule sialoadhesin (Sn) [10].
• The tissue distribution as well as the in vitro expression of the ED3 antigen and of the sheep erythrocyte receptor (SER), binding unopsonized erythrocytes in the mouse, are very similar [11].
• As we reported previously, compared with CO mice, FR and SER minimally influenced the gene expression profiles; however, 345 transcripts of 6,266 genes determined to be expressed in WAT were significantly altered by LER [12].
• The maximum SER' in these 13 tumours did not depend on histology or regrowth rate [13].

Anatomical context of Siglec1

• Macrophage subpopulations in the mouse express a lectin-like receptor, sialoadhesin (originally named sheep erythrocyte receptor, SER), which selectively recognizes sialoglycoconjugates and is likely to be involved in cellular interactions of stromal macrophages in haematopoietic and lymphoid tissues [14].
• B- and T-cell maturation as well as responses to stimulation with thioglycolate were only slightly affected by Sn deficiency [15].
• Analysis of cell populations revealed no differences in bone marrow, peritoneal cavity, and thymus, but there was a small increase in CD8 T cells and a decrease in B220-positive cells in spleens and lymph nodes of Sn-deficient mice [15].
• Siglec-1-positive macrophages in humans are found primarily in the perifollicular zone, whereas in chimpanzees they also occur in the marginal zone and surrounding the periarteriolar lymphocyte sheaths [16].
• Sialoadhesin is a sialic acid-binding immunoglobulin-like lectin (Siglec), expressed on subsets of macrophages [17].

Associations of Siglec1 with chemical compounds

• These results provide the first direct measurement of the affinity of sialoadhesin for sialosides and confirm the critical importance of the conserved arginine in interactions between sialosides and members of the siglec family of sialic acid-binding, immunoglobulin-like lectins [18].
• BSO increased the maximum SER for SR 2508 (3 mM/fraction) from 1.2 to 1.4 in the RIF tumor, and from 1.4 to 1.8 in the MCA tumor [19].
• The SER of 0.01 mM and 0.05 mM BSO for 24 h under the hypoxic condition is 1.21 and 1.36, respectively [20].
• 3. Band 4 cells exhibited a 1D0 of 5.15 Gy to radiation only and 2.75 Gy to radiation plus misonidazole (SER of 1.9) [21].
• SER values (with 95% confidence limits) were 1.28 (1.20-1.37) for 240 mg/kg SR 2508, 1.20 (1.10-1.30) for 240 mg/kg Ro 03-8799, 1.46 (1.33-1.59) for 240 mg/kg of both drugs in combination, 1.46 (1.38-1.55) for 480 mg/kg SR 2508 and 1.46 (1.31-1.62) for 480 mg/kg Ro 03-8799 [22].

Other interactions of Siglec1

• Sialoside specificity of the siglec family assessed using novel multivalent probes: identification of potent inhibitors of myelin-associated glycoprotein [23].
• During ontogeny, the appearance and organization of the MARCO-expressing cells in the spleen precedes the appearance of other receptors on macrophages in the marginal zone, such as SIGNR1 and Siglec-1 [24].
• Resident bone marrow macrophages in hematopoietic clusters have previously been shown to express a novel lectin-like sheep erythrocyte receptor, SER, which mediates binding of unopsonized sheep erythrocytes via recognition of sialylated glycoconjugates and may interact with sialylated ligands on murine bone marrow cells [25].
• Thymus-derived features were identified on the membrane of the neoplastic lymphocytes using the following cellsurface markers: Heterologous T-cell antigen, sheep erythrocyte receptor, surface immunoglobulin, complement receptor, Fc receptor and mouse erythrocyte receptor [26].

Analytical, diagnostic and therapeutic context of Siglec1

• In order to investigate its function, we generated Sn-deficient mice and confirmed that these mice are true nulls by fluorescence-activated cell sorter analysis and immunohistochemistry [15].
• SER therefore appeared to be expressed on certain M phi populations embedded in solid tissues but was largely absent from M phi recoverable by lavage [27].
• In the present study using mouse serum-induced thioglycollate-elicited peritoneal M phi (TPM) as a model system for SER expression, mAb SER-4 IgG2a completely blocked rosette formation at 1 microgram/ml [8].
• In this study, the distribution of SER on macrophages within hematopoietic clusters was localized by a monoclonal antibody, SER-4, by immunofluorescence and immunoelectron microscopy [25].
• Using flow cytometry of Sn-transfected cells and staining of lymphoid tissue sections from Sn-deficient mice, we demonstrate here that the antigen recognized by MOMA-1 is Sn [28].

References