Disease relevance of SIGLEC9

• Inflammatory neutrophils obtained from patients with acute septic shock or rheumatoid arthritis demonstrated increased Siglec-9, but normal Fas receptor-mediated cytotoxic responses when compared with normal blood neutrophils [1].

High impact information on SIGLEC9

• Anti- Siglec-9 autoantibody-depleted IVIg failed to induce this caspase-independent neutrophil death [2].
• In this study, we demonstrate that sialic acid-binding Ig-like lectin 9 (Siglec) represents a surface molecule on neutrophils that is activated by IVIg, resulting in caspase-dependent and caspase-independent forms of cell death [2].
• The combined results demonstrate that both Siglec-7 and Siglec-9 are capable of negative regulation of TCR signaling and that ligand binding is required for optimal activity [3].
• Cloning, characterization, and phylogenetic analysis of siglec-9, a new member of the CD33-related group of siglecs. Evidence for co-evolution with sialic acid synthesis pathways [4].
• Binding assays showed that, similar to Siglec-7, Siglec-9 recognized sialic acid in either the alpha2,3- or alpha2, 6-glycosidic linkage to galactose [5].

Biological context of SIGLEC9

• In normal neutrophils, Siglec-9 ligation induced apoptosis [1].
• A full-length cDNA encoding Siglec-9 was isolated from a dibutyryl cAMP-treated HL-60 cell cDNA library [5].
• Overall, Siglec-9 is approximately 80% identical in amino acid sequence to Siglec-7, suggesting that the genes encoding these two proteins arose relatively recently by gene duplication [5].
• The siglec-9 gene is composed of seven exons, with six intervening introns [6].
• It is located on chromosome 19q13.4, approximately 330 kb downstream of the Siglec9 gene [7].

Anatomical context of SIGLEC9

• Taken together, these data suggest that apoptotic (ROS- and caspase-dependent) and nonapoptotic (ROS-dependent) death pathways are initiated in neutrophils via Siglec-9 [1].
• Siglec-9 is expressed on granulocytes and monocytes [4].
• Siglec-9, a novel sialic acid binding member of the immunoglobulin superfamily expressed broadly on human blood leukocytes [5].
• A small region of the natural killer cell receptor, Siglec-7, is responsible for its preferred binding to alpha 2,8-disialyl and branched alpha 2,6-sialyl residues. A comparison with Siglec-9 [8].
• Based on reports of the presence of these siglecs on T cells, we sought to determine if they are capable of modulating T cell receptor (TCR) signaling using Jurkat T cells stably and transiently transfected with Siglec-7 or Siglec-9 [3].

Associations of SIGLEC9 with chemical compounds

• Siglec-9 is predicted to contain three extracellular immunoglobulin-like domains that comprise an N-terminal V-set domain and two C2-set domains, a transmembrane region and a cytoplasmic tail containing two putative tyrosine-based signaling motifs [5].
• Binding studies on recombinant human Siglec-9 show recognition of both Neu5Ac and Neu5Gc [9].

Regulatory relationships of SIGLEC9

• Interestingly, human intravenous immunoglobulin (IVIg) preparations contain natural anti-Siglec-9 autoantibodies, which are able to ligate Siglec-9 on neutrophils and induce autophagic-like cell death in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and some other survival cytokines [10].

Other interactions of SIGLEC9

• Identification and molecular characterization of a novel member of the siglec family (SIGLEC9) [6].
• A double mutant (P439S, N458T) or triple mutant (I435L, P439S, N458T) recruited SHPs as much as did Siglec-9, indicating that Pro439 in the proximal motif and Asn458 in the distal motif of Siglec-7 attenuate its ability to recruit phosphatases [11].
• In this study, we applied a panel of immunologic and cell-based assays to demonstrate that GBS of several serotypes interacts in a Sia- and serotype-specific manner with certain human CD33rSiglecs, including hSiglec-9 and hSiglec-5 expressed on neutrophils and monocytes [12].

Analytical, diagnostic and therapeutic context of SIGLEC9

• Through RT-PCR, we have examined the expression of siglec-9 in a large number of tissues and have found relatively high-level expression in bone marrow, placenta, spleen, and fetal liver [6].

References