This communication is concerned with the binding specificity of the
leukocyte-adhesion molecule L-selectin (leukocyte homing receptor) towards structurally defined sulphated
oligosaccharides of the
blood group Le(a) and Le(x) series, and of the
glycosaminoglycan 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
Le(a)/Le(x) 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 Le(a) and Le(x) 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-
acetylgalactosamine,
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-containing
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 possibility 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.