BIOMAT Database Logo BIOMAT Database Logo

L-selectin ligands in rat high endothelium: multivalent sialyl Lewis x glycans are high-affinity inhibitors of lymphocyte adhesion. 1997

S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Haartman Institute, Department of Bacteriology and Immunology, University of Helsinki, Finland.

Lymphocyte homing is initiated by their tethering to and rolling on the high endothelium and is followed by extravasation into the lymph nodes. We show here that glycosylated cell adhesion molecule-1 (GlyCAM-1), CD34, and sialyl Lewis x (sLex) are present on rat lymph node high endothelium analyzed by using monoclonal antibodies. alpha (1,3)fucosyltransferase VII (Fuc-TVII), the last enzyme involved in the synthesis of the sLex sequence is also expressed on the rat lymph node high endothelium. We have synthesized a family of sLex-decorated oligosaccharide structures and used them to inhibit lymphocyte binding to high endothelium in the Stamper-Woodruff assay. Monovalent sLex, branched di- and tetravalent sLex, as well as a linear tetravalent sLex significantly reduce lymphocyte binding to endothelium. The branched and linear forms of tetravalent sLex were clearly superior inhibitors of the L-selectin-dependent lymphocyte adhesion, with IC50 values in low nanomolar range. In contrast, the fucose-free analogs having the same charge and approximately the same size as the corresponding sLex glycans had no effect on lymphocyte binding and served as negative controls. Taken together, these data show the crucial importance of sLex in the endothelial ligands for L-selectin. Furthermore, we suggest that L-selectin acts as an oligomer on the lymphocyte surface as it binds multivalent sLex glycans.

UI MeSH Term Description Entries
D007983 Lewis Blood Group Antigens Carbohydrate antigens structurally related to the ABH BLOOD-GROUP SYSTEM. They may occur as a modification of saccharide chains on glycolipids or glycoproteins on cell surfaces or in plasma, or as free oligosaccharides in secretions. Lewis antigens are not synthesized in blood cells. Instead Lewis glycolipids present in plasma are absorbed onto the surface of ERYTHROCYTES; LYMPHOCYTES; and PLATELETS. The phenotypes Le(a) and Le(b) are the result of the actions of two genes the Le gene (fucosyltransferase FUT3) and the Se gene (fucosyltransferase FUT2) on the precursor carbohydrate, glycolipid or glycoprotein. Other FUCOSYLTRANSFERASES can also synthesize the Lewis antigens. Blood Group Lewis Related Antigens,Lewis Antigen Related Tumor-Associated Antigens,Lewis Antigens,Lewis Blood Group Related Antigens,Lewis Blood Group Related Tumor-Associated Antigens,Lewis Blood-Group System,Lewis Related Antigens,Lewis System,Sialyl Lewis Antigens,Le Antigens,Le(a) Blood Group System,Antigens, Lewis,Antigens, Lewis Related,Antigens, Sialyl Lewis,Blood-Group System, Lewis,Lewis Antigen Related Tumor Associated Antigens,Lewis Blood Group Related Tumor Associated Antigens,Lewis Blood Group System
D008198 Lymph Nodes They are oval or bean shaped bodies (1 - 30 mm in diameter) located along the lymphatic system. Lymph Node,Node, Lymph,Nodes, Lymph
D008214 Lymphocytes White blood cells formed in the body's lymphoid tissue. The nucleus is round or ovoid with coarse, irregularly clumped chromatin while the cytoplasm is typically pale blue with azurophilic (if any) granules. Most lymphocytes can be classified as either T or B (with subpopulations of each), or NATURAL KILLER CELLS. Lymphoid Cells,Cell, Lymphoid,Cells, Lymphoid,Lymphocyte,Lymphoid Cell
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011485 Protein Binding The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments. Plasma Protein Binding Capacity,Binding, Protein
D002240 Carbohydrate Sequence The sequence of carbohydrates within POLYSACCHARIDES; GLYCOPROTEINS; and GLYCOLIPIDS. Carbohydrate Sequences,Sequence, Carbohydrate,Sequences, Carbohydrate
D002448 Cell Adhesion Adherence of cells to surfaces or to other cells. Adhesion, Cell,Adhesions, Cell,Cell Adhesions
D004729 Endothelium, Lymphatic Unbroken cellular lining (intima) of the lymph vessels (e.g., the high endothelial lymphatic venules). It is more permeable than vascular endothelium, lacking selective absorption and functioning mainly to remove plasma proteins that have filtered through the capillaries into the tissue spaces. Lymphatic Endothelium,Endotheliums, Lymphatic,Lymphatic Endotheliums
D005732 Gangliosides A subclass of ACIDIC GLYCOSPHINGOLIPIDS. They contain one or more sialic acid (N-ACETYLNEURAMINIC ACID) residues. Using the Svennerholm system of abbrevations, gangliosides are designated G for ganglioside, plus subscript M, D, or T for mono-, di-, or trisialo, respectively, the subscript letter being followed by a subscript arabic numeral to indicated sequence of migration in thin-layer chromatograms. (From Oxford Dictionary of Biochemistry and Molecular Biology, 1997) Ganglioside,Sialoglycosphingolipids
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Multivalent sialyl Lewis x ligands of definite structures as inhibitors of E-selectin mediated cell adhesion.
April 1998, Glycobiology,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Synthesis of a tetravalent sialyl Lewis x glycan, a high-affinity inhibitor of L-selectin-mediated lymphocyte binding to endothelium.
January 1996, Glycobiology,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers.
February 2017, Biology,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Endothelial-selectin ligands sialyl Lewis(x) and sialyl Lewis(a) are differentiation antigens immunogenic in human melanoma.
May 1997, Cancer,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
In vitro experimental studies of sialyl Lewis x and sialyl Lewis a on endothelial and carcinoma cells: crucial glycans on selectin ligands.
August 1997, Glycoconjugate journal,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
De novo expression of endothelial sialyl Lewis(a) and sialyl Lewis(x) during cardiac transplant rejection: superior capacity of a tetravalent sialyl Lewis(x) oligosaccharide in inhibiting L-selectin-dependent lymphocyte adhesion.
October 1995, The Journal of experimental medicine,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Endothelial sialyl Lewis x as a crucial glycan decoration on L-selectin ligands.
January 1998, Advances in experimental medicine and biology,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Synthesis of a new nanomolar saccharide inhibitor of lymphocyte adhesion: different polylactosamine backbones present multiple sialyl Lewis x determinants to L-selectin in high-affinity mode.
June 1997, Glycobiology,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Syntheses of 6-sulfo sialyl Lewis X glycans corresponding to the L-selectin ligand "sulfoadhesin".
July 2004, Organic letters,
S Toppila, and J Lauronen, and P Mattila, and J P Turunen, and L Penttilä, and T Paavonen, and O Renkonen, and R Renkonen
Endothelial sulfated sialyl Lewis x glycans, putative L-selectin ligands, are preferentially expressed in bronchial asthma but not in other chronic inflammatory lung diseases.
October 2000, American journal of respiratory cell and molecular biology,
Copied contents to your clipboard!