Further studies of the binding specificity of the leukocyte adhesion molecule, L-selectin, towards sulphated oligosaccharides—suggestion of a link between the selectin- and the integrin-mediated lymphocyte adhesion systems

• Published in: Glycobiology (Oxford) 1995-02, Vol.5 (1), p.29-38
• Main Authors: Green, Paula J., Yuen, Chun-Ting, Childs, Robert A., Chai, Wengang, Miyasaka, Masayuki, Lemoine, Remy, Lubineau, André, Smith, Brian, Ueno, Hiroaki, Nicolaou, Kyriacos C., Feizi, Ten
• Format: Article
• Language: English
• Subjects: Animals; Carbohydrate Conformation; Carbohydrate Sequence; Cell Adhesion - physiology; Cell Adhesion Molecules - metabolism; Cell Adhesion Molecules - physiology; Endothelium - physiology; glycosaminoglycans; Integrins - physiology; Kinetics; L-Selectin; leukocyte adhesion cascades; Lymphocytes - physiology; Models, Biological; Molecular Sequence Data; neoglycolipids; oligosaccharide presentation; Oligosaccharides - chemistry; Oligosaccharides - metabolism; Rats; Recombinant Proteins - metabolism; Substrate Specificity; Sulfuric Acids - metabolism; sulphated oligosaccharides
• ISSN: 0959-6658; 1460-2423
• DOI: 10.1093/glycob/5.1.29

This communication is concerned with the binding specficity of the leukocyte-adhesion molecule L-selectin (leukocyte homing receptor) towards structurally defined sulphated oligosaccharides of the blood group Lea and Lex series, and of the glycolsaminoglycan series heparin, chondroitin sulphate and keratan sulphate. The recombinant soluble form of the rat L-selectin (L-selectin-IgG Fc chimera) investigated here was shown previously to bind to lipid-linked oligosaccharides 3-O, 4-O and 6-O sulphated at galactose, such as sulphatides and a mixture of 3-sulphated Lea/Lex type tetrasaccharides isolated from ovarian cystadenoma, as well as to the HNK-1 glycolipid with 3-O sulphated glucuronic acid. In the present study, the L-selectin investigated in both chromatogram binding and plastic microwell binding experiments using neoglycolipids was found to bind to the individual 3-sulphated Lea and Lex sequences (penta-, tetra- and trisaccharides), and with somewhat lower intensities to their non-fucosylated analogues. Glycosaminoglycan disaccharides of keratan sulphate, heparin and chondroitin sulphate types were also bound by L-selectin in one or both assay systems, leading to the conclusion that clustered glycosaminoglycan oligosaccharides with 6-O sulphation of N-acetylgalactctosamine, N-acetylglucosamine or glucosamine, 4-O sulphation of N-acetylgalactosamine, 2-O sulphation of uronic acid, N-sulphation of glucosamine and, to a lesser extent, the non-sulphated uronic acid-contahing disaccharides, can support L-selectin adhesion. As inflammatory chemokines (short-range stimulators of lymphocyte migration which trigger integrin activation) are known to bind to endothelial glycosaminoglycans, we propose that the binding of the lymphocyte membrane L-selectin to endothelial glycosaminoglycans may provide a link between the selectin-mediated and integrin-mediated adhesion systems in leukocyte extravasation cascades. The posibility is also raised that lymphocyte L-selectin interactions with glycosaminoglycans may contribute to pathologies of glycosaminoglycan-rich tissues, e.g. cartilage loss in rheumatoid arthritis and inflammatory lesions of the cornea.