Sialoadhesin

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Sialoadhesin
2BVE.pdb.jpg
Structure of the N-terminal domain of mouse sialoadhesin. [1]
Identifiers
SymbolSIGLEC1
Alt. symbolsSN, CD169
NCBI gene 6614
HGNC 11127
OMIM 600751
PDB 2BVE
RefSeq NM_023068
UniProt Q9BZZ2
Other data
Locus Chr. 20 p13
Search for
Structures Swiss-model
Domains InterPro

Sialoadhesin (SIGLEC-1) is a cell adhesion molecule found on the surface of macrophages. It is found in especially high amounts on macrophages of the spleen, liver, lymph node, bone marrow, colon, and lungs.

Soluble SIGLEC-1 is a biomarker of monocyte-macrophage activation in systemic lupus erythematosus (SLE) and other autoimmune disorders. [2] In patients with rheumatoid arthritis, the protein has been found in great amounts on macrophages of the affected tissues. [3] It is defined as an I-type lectin, since it contains 17 immunoglobulin (Ig) domains (one variable domain and 16 constant domains), and thus also belongs to the immunoglobulin superfamily (IgSF). Sialoadhesin binds to certain molecules called sialic acids. During this binding process a salt bridge (protein) is formed between a highly conserved arginine residue (from the v-set domain to the 3'-sialyllactose) and the carboxylate group of the sialic acid. [3] Since sialoadhesin binds sialic acids with its N-terminal IgV-domain, it is also a member of the SIGLEC family. Alternate names for sialoadhesin include siglec-1 and CD169 (cluster of differentiation 169). [4]

Sialoadhesin predominantly binds neutrophils, but can also bind monocytes, natural killer cells, B cells and a subset of cytotoxic T cells by interacting with sialic acid molecules in the ligands on their surfaces. [5]

Sialoadhesin (CD169) positive macrophages, along with mesenchymal stem cells and beta-adrenergic neurons, form the hematopoietic stem cell niche in the bone marrow. CD169+ macrophages mediate signaling between the various cells and seem to promote hematopoietic stem cell retention to the niche. Siglec-1 is also expressed on lymph node subcapsular sinus macrophages. Research using a murine melanoma model has demonstrated that these subcapsular sinus macrophages bind to sialylated proteins present on the surface of pioneer metastatic cells shortly after their landing in the lymph nodes. This interaction serves as a critical step in metastatic colonization, providing a conducive environment, or 'soil,' for the establishment and proliferation of pioneer metastatic cells, often referred to as 'seeds.' [6]

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<span class="mw-page-title-main">CD32</span> Surface receptor glycoprotein

CD32, also known as FcγRII or FCGR2, is a surface receptor glycoprotein belonging to the Ig gene superfamily. CD32 can be found on the surface of a variety of immune cells. CD32 has a low-affinity for the Fc region of IgG antibodies in monomeric form, but high affinity for IgG immune complexes. CD32 has two major functions: cellular response regulation, and the uptake of immune complexes. Cellular responses regulated by CD32 include phagocytosis, cytokine stimulation, and endocytic transport. Dysregulated CD32 is associated with different forms of autoimmunity, including systemic lupus erythematosus. In humans, there are three major CD32 subtypes: CD32A, CD32B, and CD32C. While CD32A and CD32C are involved in activating cellular responses, CD32B is inhibitory.

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<span class="mw-page-title-main">CD22</span> Lectin molecule

CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases.

<span class="mw-page-title-main">CD33</span> Mammalian protein found in Homo sapiens

CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.

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<span class="mw-page-title-main">SIGLEC7</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 7 is a protein that in humans is encoded by the SIGLEC7 gene. SIGLEC7 has also been designated as CD328.

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Sialic acid-binding Ig-like lectin 12, or Siglec-XII, is a protein that in humans, is encoded by the SIGLEC12 gene.

<span class="mw-page-title-main">SIGLEC5</span> Protein-coding gene in the species Homo sapiens

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<span class="mw-page-title-main">SIGLEC8</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 8 is a protein that in humans is encoded by the SIGLEC8 gene. This gene is located on chromosome 19q13.4, about 330 kb downstream of the SIGLEC9 gene. Within the siglec family of transmembrane proteins, Siglec-8 belongs to the CD33-related siglec subfamily, a subfamily that has undergone rapid evolution.

<span class="mw-page-title-main">SIGLEC10</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 10 is a protein that in humans is encoded by the SIGLEC10 gene. Siglec-G is often referred to as the murine paralog of human Siglec-10

<span class="mw-page-title-main">FCAR</span> Mammalian protein found in Homo sapiens

Fc fragment of IgA receptor (FCAR) is a human gene that codes for the transmembrane receptor FcαRI, also known as CD89. FcαRI binds the heavy-chain constant region of Immunoglobulin A (IgA) antibodies. FcαRI is present on the cell surface of myeloid lineage cells, including neutrophils, monocytes, macrophages, and eosinophils, though it is notably absent from intestinal macrophages and does not appear on mast cells. FcαRI plays a role in both pro- and anti-inflammatory responses depending on the state of IgA bound. Inside-out signaling primes FcαRI in order for it to bind its ligand, while outside-in signaling caused by ligand binding depends on FcαRI association with the Fc receptor gamma chain.

The following outline is provided as an overview of and topical guide to immunology:

Lymph node stromal cells are essential to the structure and function of the lymph node whose functions include: creating an internal tissue scaffold for the support of hematopoietic cells; the release of small molecule chemical messengers that facilitate interactions between hematopoietic cells; the facilitation of the migration of hematopoietic cells; the presentation of antigens to immune cells at the initiation of the adaptive immune system; and the homeostasis of lymphocyte numbers. Stromal cells originate from multipotent mesenchymal stem cells.

<span class="mw-page-title-main">Sialic acid binding ig-like lectin 15</span> Protein-coding gene in the species Homo sapiens

Sialic acid binding Ig-like lectin 15 (Siglec-15) is a protein that in humans is encoded by the SIGLEC15 gene. Siglec-15 is predominately expressed on osteoclasts, elevated levels of Siglec- 15 in the bone metastatic niche can promote tumor-induced osteoclastogenesis as well as suppress antigen-specific T cell responses. Researchers demonstrated that antibody blockade of the Siglec-15/sialic acid glycol-immune checkpoint axis can act as a potential treatment for breast cancer bone metastasis.

Lirentelimab is a humanized nonfucosylated monoclonal antibody that targets sialic acid-binding Ig-like lectin 8 (SIGLEC8). In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis. Adverse reactions include infusion reactions, which are mild to moderate and typically occur following the first infusion.

<span class="mw-page-title-main">Paired receptors</span>

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<span class="mw-page-title-main">SIGLEC6</span> Protein-coding gene in the species Homo sapiens

Sialic acid-binding Ig-like lectin 6 is a protein that in humans is encoded by the SIGLEC6 gene. The gene was originally named CD33L (CD33-like) due to similarities between these genes but later became known as OB-BP1 due to its ability to bind to this factor and, finally, SIGLEC6 as the sixth member of the SIGLEC family of receptors to be identified. The protein has also been given the CD designation CD327.

References

  1. PDB: 2BVE ; Zaccai NR, May AP, Robinson RC, Burtnick LD, Crocker PR, Brossmer R, Kelm S, Jones EY (February 2007). "Crystallographic and in silico analysis of the sialoside-binding characteristics of the Siglec sialoadhesin". J. Mol. Biol. 365 (5): 1469–79. doi:10.1016/j.jmb.2006.10.084. PMID   17137591.
  2. Oliveira, João J.; Karrar, Sarah; Rainbow, Daniel B.; Pinder, Christopher L.; Clarke, Pamela; Rubio García, Arcadio; Al-Assar, Osama; Burling, Keith; Morris, Sian; Stratton, Richard; Vyse, Tim J.; Wicker, Linda S.; Todd, John A.; Ferreira, Ricardo C. (2018-07-27). "The plasma biomarker soluble SIGLEC-1 is associated with the type I interferon transcriptional signature, ethnic background and renal disease in systemic lupus erythematosus". Arthritis Research & Therapy. 20 (1): 152. doi: 10.1186/s13075-018-1649-1 . ISSN   1478-6362. PMC   6062988 . PMID   30053827.
  3. 1 2 Hartnell A, Steel J, Turley H, Jones M, Jackson DG, Crocker PR (January 2001). "Characterization of human sialoadhesin, a sialic acid binding receptor expressed by resident and inflammatory macrophage populations". Blood. 97 (1): 288–96. doi: 10.1182/blood.V97.1.288 . PMID   11133773.
  4. Varki A (2001-09-10). "Sialoadhesin, Siglec-1 (CD169)". Protein Reviews on the Web (PROW) Guide. United States National Center for Biotechnology Information (NCBI). Archived from the original on 2007-07-01. Retrieved 2011-04-15.
  5. Kelm S, Pelz A, Schauer R, Filbin M, Tang S, de Bellard M, Schnaar R, Mahoney J, Hartnell A, Bradfield P (1994). "Sialoadhesin, myelin-associated glycoprotein and CD22 define a new family of sialic acid-dependent adhesion molecules of the immunoglobulin superfamily". Curr Biol. 4 (11): 965–72. Bibcode:1994CBio....4..965K. doi:10.1016/S0960-9822(00)00220-7. PMID   7533044. S2CID   20282803.
  6. Singh R, Choi BK (2019). "Siglec1-expressing subcapsular sinus macrophages provide soil for melanoma lymph node metastasis". eLife. 8: e48916. doi: 10.7554/eLife.48916 . PMC   6930078 . PMID   31872800. S2CID   209461892.