FURTHER-STUDIES OF THE BINDING-SPECIFICITY OF THE LEUKOCYTE ADHESION MOLECULE, L-SELECTIN, TOWARDS SULFATED OLIGOSACCHARIDES - SUGGESTION OF A LINK BETWEEN THE SELECTIN-MEDIATED AND THE INTEGRIN-MEDIATED LYMPHOCYTE ADHESION SYSTEMS

This communication is concerned with the binding specificity of the le ukocyte-adhesion molecule L-selectin (leukocyte homing receptor) towar ds structurally defined sulphated oligosaccharides of the blood group Le(a) and Le(x) series, and of the glycosaminoglycan series heparin, c hondroitin sulphate and keratan sulphate, The recombinant soluble form of the rat L-selectin (L-selectin-IgG Fc chimera) investigated here w as 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 Le(a)/Le(x) type tetrasaccharides isolated from ovarian cys tadenoma, as well as to the HNK-1 glycolipid with 3-O sulphated glucur onic acid, In the present study, the L-selectin investigated in both c hromatogram binding and plastic microwell binding experiments using ne oglycolipids was found to bind to the individual 3-sulphated Le(a) and Le(x) sequences (penta-, tetra- and trisaccharides), and with somewha t lower intensities to their non-fucosylated analogues, Glycosaminogly can disaccharides of keratan sulphate, heparin and chondroitin sulphat e types were also bound by L-selectin in one or both assay systems, le ading to the conclusion that clustered glycosaminoglycan oligosacchari des with 6-O sulphation of N-acetylgalactosamine, N-acetylglucosamine or glucosamine, 4-O sulphation of N-acetylgalactosamine, 2-O sulphatio n of uronic acid, N-sulphation of glucosamine and, to a lesser extent, the non-sulphated uronic acid-containing disaccharides, can support L -selectin adhesion, As inflammatory chemokines (short-range stimulator s of lymphocyte migration which trigger integrin activation) are known to bind to endothelial glycosaminoglycans, we propose that the bindin g of the lymphocyte membrane L-selectin to endothelial glycosaminoglyc ans may provide a link between the selectin-mediated and integrin-medi ated adhesion systems in leukocyte extravasation cascades, The possibi lity is also raised that lymphocyte L-selectin interactions with glyco saminoglycans may contribute to pathologies of glycosaminoglycan-rich tissues, e.g. cartilage loss in rheumatoid arthritis and inflammatory lesions of the cornea.