発現細胞

好中球、好酸球、単球

機能

糖脂質や多くの細胞表面糖タンパクに発現している末端の3糖

別名

Lewis^x, Le^x

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2019/06/25 00:47:12」(JST)

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[Wiki en表示]

Sialyl Lewis^X, also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide carbohydrate which is usually attached to O-glycans on the surface of cells. It is known to play a vital role in cell-to-cell recognition processes. It is also the means by which an egg attracts sperm; first, to stick to it, then bond with it and eventually form a zygote. The discovery of the essential role that this tetrasaccharide plays in the fertilization process was reported in August 2011.^[1]

Sialyl Lewis ^X is also one of the most important blood group antigens and is displayed on the terminus of glycolipids that are present on the cell surface. The sialyl Lewis ^X determinant, E-selectin ligand carbohydrate structure, is constitutively expressed on granulocytes and monocytes and mediates inflammatory extravasation of these cells. Resting T- and B-lymphocytes lack its expression and are induced to strongly express sialyl Lewis ^X upon activation. The sialyl Lewis ^X determinant is expressed preferentially on activated Th1 cells but not on Th2 cells.

Structure

Sialyl-Lewis X is a tetrasaccharide composed of a sialic acid, fucose and an N-acetyllactosamine. Its sytematic name is 5-acetylneuraminyl-(2-3)-galactosyl-(1-4)-(fucopyranosyl-(1-3))-N-acetylglucosamine (Neu5Acα2-3Galβ1-4[Fucα1-3]GlcNAcβ). In humans, it is synthesized by two fucosyltransferases: FUT4 and FUT9.^[2]

Function

Leukocyte homing

Sialyl-Lewis^x is important in leukocyte tethering and rolling. Leukocytes move through the blood stream and then tether themselves to the endothelial wall and roll along the endothelial tissue to determine if they want to leave the bloodstream to get to necessary tissue. Sialyl-Lewis^x is a necessary partner for the three selectins that bind the leukocyte and endothelial cells. When sialyl-Lewis^x is part of an O-glycan and attached to CD34 it can then bind to L-selectin. For the binding to L-selectin to occur sialyl-Lewis^x must undergo sulfation. For sialyl-Lewis^x to bind to P-selectin, an O-linked glycan near the N-terminus of P-Selectin Glycoprotein Ligand-1 (PSGL-1) is modified with sialyl-Lewis^x and in combination with nearby tyrosine residues modified with sulfate, forms the binding contact for P-selectin. For sialyl-Lewis^x to bind to E-selectin it can be part of either an N-linked or O-linked glycan attached to cell surface glycoproteins such as PSGL-1, CD43 or CD44. This sialyl-Lewis^x mediated binding to selectins allows circulating leukocytes to stick to and roll along endothelial cells lining blood vessels thereby enabling the leukocytes to accumulate at a site of vascular inflammation.

Fertilization

Sialyl-Lewis^x allows a sperm cell to recognize and fertilize an egg cell. For fertilization to occur, human sperm must bind to the zona pellucida (ZP), the translucent matrix covering the human egg composed of four glycoproteins ZP1, 2, 3, and 4, and transit through the matrix in order to fuse with the oocyte.^[3] Human ZP is coated with highly dense N- and O-glycans that are terminated with the sialyl-Lewis^x sequence.^[1] The hemizona assay, which assesses sperm-ZP binding by counting the number of sperm bound to hemispheres of bisected nonliving human eggs in vitro, revealed that as little as 0.5 mM sialyl-Lewis^x inhibits sperm-ZP binding by 63%.^[1] Furthermore, adding purified and solubilized ZP3 or ZP4 from the human oocyte dose-dependently inhibits sperm-ZP binding in the hemizona assay.^[4] Such evidence suggest that the early steps of human sperm-egg binding may be mediated by lectins for sialyl-Lewis^x present on human sperm.

Clinical significance

Leukocyte adhesion deficiency

Defective synthesis of the sialyl Lewis ^X antigen results in immunodeficiency (leukocyte adhesion deficiency type 2). Defective synthesis can be caused by the loss of fucosyltransferase, impairing the glycosylation of the glycosphingolipid. Sialyl Lewis x is being researched for detection and treatment of immune disorders because of its presence on leukocytes.

Blood cancers

Sialyl-Lewis^x mediates phagocytosis and chemotaxis, found on neutrophils;^[5] expressed in patients with Hodgkin disease, some B-cell chronic lymphocytic leukemias, acute lymphoblastic leukemias, and most acute nonlymphocytic leukemias. CD15 is present on almost all Reed–Sternberg cells, including their rare mononuclear variants, and, as such, can be used in immunohistochemistry to identify the presence of such cells in biopsies. The presence of these cells is diagnostic of Hodgkin's lymphoma. Reed-Sternberg cells display a characteristic pattern of Sialyl-Lewis^x (CD15) positivity, with membranous staining combined with staining of the Golgi apparatus. Immunohistochemical panels for the diagnosis of Hodgkins disease typically employ CD15 along with CD30 and CD45; the latter does not stain Reed-Sternberg cells, but does stain almost all other lymphoid cells. Sialyl-Lewis^x is also present in about 50% of adenocarcinoma cells and can be used to distinguish such conditions from mesothelioma, which is typically negative.^[6]

Cancer metastasis

Sialyl-Lewis^x plays a critical role in cancer metastasis, facilitating the extravasation of cancer cells out of the bloodstream while they are moving through the body. Therefore, sialyl Lewis x is being used as a target in studies to fight tumors and cancer cell growth. It has been shown that there is frequent overexpression of sialyl Lewis x on cancer cells and is found on both N-glycan and O-glycans. Sialyl Lewis x is being researched with CD markers to find new ways to create biosensors for cancer cells. Also, it is being used in new ways to target cancer cells specifically for cancer treatment.

In vitro fertilization

Sialyl-Lewis^x is being used to achieve greater rates of fertilization of eggs in women by coating the eggs with sialyl Lewis x.

Immunity and inflammation

It plays a key role in the inflammatory response and may be used to increase the leukocyte response to infections. Sialyl Lewis x is also an inflammation-associated antigen on liver cells. It becomes over expressed on diseased liver cells and can be used as a way to detect liver disease in a patient.

History

The term Lewis in its name comes from the name of a family of people who suffered from a red blood cell incompatibility. The studies done on these individuals' red blood cells led to the discovery of sialyl Lewis X. Sialyl Lewis x is a very important red blood cell antigen present on the glycolipids on the plasma membrane of the cell.

Its localization on the cell surface of cells led to its alternative nomenclature as a cluster of differentiation. Clusters of differentiation are a naming system devised in 1982 to classify cell-surface antigens on leukocytes identified via monoclonal antibodies. Sialyl Lewis X was assigned the name CD15.

References

^ ^a ^b ^c Pang, Poh-Choo; Chiu, Philip C. N.; et al. (18 August 2011). "Human Sperm Binding Is Mediated by the Sialyl-Lewisx Oligosaccharide on the Zona Pellucida". Science. 333 (6050): 1761–1764. doi:10.1126/science.1207438. PMID 21852454.
^ Nakayama F, Nishihara S, Iwasaki H, Kudo T, Okubo R, Kaneko M, Nakamura M, Karube M, Sasaki K, Narimatsu H (May 2001). "CD15 expression in mature granulocytes is determined by alpha 1,3-fucosyltransferase IX, but in promyelocytes and monocytes by alpha 1,3-fucosyltransferase IV". J. Biol. Chem. 276 (19): 16100–6. doi:10.1074/jbc.M007272200. PMID 11278338.
^ Clark, G. F. (2013). "The role of carbohydrate recognition during human sperm-egg binding". Human Reproduction. 28 (3): 566–577. doi:10.1093/humrep/des447. PMID 23315069.
^ Chiu, P. C. N.; Wong, B. S. T.; Chung, M. -K.; Lam, K. K. W.; Pang, R. T. K.; Lee, K. -F.; Sumitro, S. B.; Gupta, S. K.; Yeung, W. S. B. (2008). "Effects of Native Human Zona Pellucida Glycoproteins 3 and 4 on Acrosome Reaction and Zona Pellucida Binding of Human Spermatozoa". Biology of Reproduction. 79 (5): 869–877. doi:10.1095/biolreprod.108.069344. PMID 18667750.
^ Kerr MA, Stocks SC (November 1992). "The role of CD15-(Le(X))-related carbohydrates in neutrophil adhesion". Histochem. J. 24 (11): 811–26. doi:10.1007/BF01046353. PMID 1362195.
^ Leong, Anthony S-Y; Cooper, Kumarason; Leong, F Joel W-M (2003). Manual of Diagnostic Cytology (2nd ed.). Greenwich Medical Media, Ltd. pp. 83–84. ISBN 1-84110-100-1.

UpToDate Contents

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1. 結節性リンパ球優位型ホジキンリンパ腫の臨床症状、病理学的特徴、および診断clinical manifestations pathologic features and diagnosis of nodular lymphocyte predominant hodgkin lymphoma [show details]
…classic HL are typically CD15+, CD30+, CD45- (leukocyte common antigen), CD20-. In contrast, the L&H cells of NLPHL are CD45+, BCL6+, CD19+, CD20+, CD22+, CD79a+, BCL6+, and CD15-; they only rarely express …
2. 原発性免疫不全症の診断のためのフローサイトメトリーflow cytometry for the diagnosis of primary immunodeficiencies [show details]
…is stained with antibodies to CD15 (a neutrophil antigen) and CD14 (a monocyte antigen), three populations of cells are detected: a population of cells that only express CD15 (neutrophils), a population …
3. Pathogenesis of Hodgkin lymphomapathogenesis of hodgkin lymphoma [show details]
…express CD30 and CD15, and lack CD45 . This immunophenotype is distinctive because CD45 (also known as leukocyte common antigen [LCA]) is expressed by almost all other types of lymphoid cells; CD15 is usually…
4. びまん性大細胞型B細胞性リンパ腫の疫学、臨床症状、病理学的特徴、および診断epidemiology clinical manifestations pathologic features and diagnosis of diffuse large b cell lymphoma [show details]
…distinguished by expression of markers that are specific for classical forms of Hodgkin lymphoma, such as CD15 and CD30, and the presence of Epstein-Barr virus, which can be detected in 40 percent of lymphocyte …
5. B細胞性急性リンパ性白血病/リンパ腫の臨床症状、病理学的特徴、診断clinical manifestations pathologic features and diagnosis of b cell acute lymphoblastic leukemia lymphoma [show details]
…typically manifest a pro-B immunophenotype (CD19+, CD10-), often with coexpression of the myeloid markers CD15, CD33, and CD68 . B-ALL with KMT2A rearrangement is associated with a poor prognosis . Leukemias…

English Journal

The Incidence and Immunophenotypic and Genetic Features of JL1 Expressing Cells and the Therapeutic Potential of an Anti-JL1 Antibody in Pediatric Acute Leukemias.

Park SH, You E, Park CJ, Jang S, Cho YU, Yoon CH, Koh KN, Im HJ, Seo JJ.
Annals of laboratory medicine. 2019 Jul;39(4)358-366.
JL1 is a newly identified CD43 epitope that specifically recognizes leukemic cells. We analyzed the incidence of JL1 expression and compared the clinical, immunophenotypic, and genetic characteristics of pediatric acute leukemia patients with respect to JL1 expression status to determine the therap
PMID 30809981

Distinctive role of dysregulated miRNAs in chordoma cancer stem-like cell maintenance.

Tuysuz EC, Gulluoglu S, Yaltirik CK, Ozbey U, Kuskucu A, Çoban EA, Sahin F, Türe U, Bayrak OF.
Experimental cell research. 2019 Jul;380(1)9-19.
Chordoma is a rare, slow-growing tumor thought to arise from remnants of embryonic notochord associated with an aggressive outcome. Cancer stem-like cells (CSCs) are related to tumorigenesis, recurrence, and resistance in cancers. Therefore, chordoma CSCs are possible targets for chordoma treatment.
PMID 30951707

A novel one-step extracellular staining for flow cytometry: Proof-of-concept on sepsis-related biomarkers.

Bourgoin P, Hayman J, Rimmelé T, Venet F, Malergue F, Monneret G.
Journal of immunological methods. 2019 Jul;470()59-63.
Flow cytometry is a powerful analytical technique. However, it requires time-consuming, multi-step sample procedure. A new protocol was developed to perform extracellular staining and red blood cell lysis in one step, using dry antibodies. Common markers of white blood cells as well as sepsis biomar
PMID 31082373

Japanese Journal

スローロリス（<i>Nycticebus coucang</i>）における上腕腺の組織学的特徴

長竿淳,野尻あゆ美,進藤順治,吉岡一機
日本野生動物医学会誌 22(4), 79-87, 2017
… 免疫組織化学的性状に関しては,上皮マーカーであるcytokeratin AE1/AE3抗体とエックリン腺マーカーであるS-100 Protein抗体ならびにCD44抗体に対して陰性で，アポクリン腺マーカーであるCD15抗体に対して陽性を示す終末部と，上皮マーカー，エックリン腺マーカー，アポクリン腺マーカーのいずれのマーカーにも陽性を示す終末部が認められた。 …
NAID 130006731442

Eva1 Maintains the Stem-like Character of Glioblastoma-Initiating Cells by Activating the Noncanonical NF-κB Signaling Pathway

Ohtsu Naoki,Nakatani Yuka,Yamashita Daisuke,Ohue Shiro,Ohnishi Takanori,Kondo Toru
Cancer research 76(1), 171-181, 2016-01
… Eva1 was prominently expressed in GICs in vitro and in stem cell marker (Sox2, CD15, CD49f)-expressing cells derived from human GBM tissues. …
NAID 120005905600

古典的ホジキンリンパ腫結節硬化型 syncytial variant の 1 例

吉野龍一,奥和子,杉生憲二,山根三千秋,原沙由美,後藤孝吉,永野輝明,中塚伸一
日本臨床細胞学会雑誌 55(4), 245-249, 2016
… 免疫染色は cytokeratin (−), LCA (−), CD30 (+), CD15 (+) を示した. …
NAID 130005421079

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★リンクテーブル★

リンク元	「悪性リンパ腫」「表面抗原分類」
拡張検索	「CD154」「CD150」
関連記事	「CD1」「CD」

「悪性リンパ腫」

Sialyl-Lewis X
Names
	Other names sialyl LeX, SLeX, CD15s, SSEA-1
Identifiers
CAS Number	98603-84-0 ;
3D model (JSmol)	Interactive image;
ChEMBL	ChEMBL375586 ;
ChemSpider	559072 ;
MeSH	sialyl+Lewis+X
PubChem CID	643990;
	InChI InChI=1S/C31H52N2O23/c1-9-18(43)21(46)22(47)28(51-9)53-24(12(5-34)32-10(2)38)25(15(42)7-36)54-29-23(48)27(20(45)16(8-37)52-29)56-31(30(49)50)4-13(40)17(33-11(3)39)26(55-31)19(44)14(41)6-35/h5,9,12-29,35-37,40-48H,4,6-8H2,1-3H3,(H,32,38)(H,33,39)(H,49,50)/t9-,12-,13-,14+,15+,16+,17+,18+,19+,20-,21+,22-,23+,24+,25+,26+,27-,28-,29-,31-/m0/s1 Key: LAQPKDLYOBZWBT-NYLDSJSYSA-N ; InChI=1/C31H52N2O23/c1-9-18(43)21(46)22(47)28(51-9)53-24(12(5-34)32-10(2)38)25(15(42)7-36)54-29-23(48)27(20(45)16(8-37)52-29)56-31(30(49)50)4-13(40)17(33-11(3)39)26(55-31)19(44)14(41)6-35/h5,9,12-29,35-37,40-48H,4,6-8H2,1-3H3,(H,32,38)(H,33,39)(H,49,50)/t9-,12-,13-,14+,15+,16+,17+,18+,19+,20-,21+,22-,23+,24+,25+,26+,27-,28-,29-,31-/m0/s1 Key: LAQPKDLYOBZWBT-NYLDSJSYBC;
	SMILES O=C(N[C@@H]1[C@@H](O)C[C@](O[C@H]1[C@H](O)[C@H](O)CO)(O[C@@H]2[C@@H](O)[C@@H](O[C@H](CO)[C@@H]2O)O[C@@H]([C@H](O[C@@H]3O[C@H]([C@@H](O)[C@@H](O)[C@@H]3O)C)[C@H](C=O)NC(=O)C)[C@H](O)CO)C(=O)O)C;
Properties
Chemical formula	C31H52N2O23
Molar mass	820.744 g/mol
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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	Infobox references

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英: malignant lymphoma
ラ: lymphoma malignum
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