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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 |
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| Authors: | Green, Paula J. Yuen, Chun-Ting Childs, Robert A. Chai, Wengang Miyasaka, Masayuki Lemoine, Remy Lubineau, Andr Smith, Brian Ueno, Hiroaki Nicolaou, Kyriacos C. Feizi, Ten |
| Affiliation: | 1The Glycobiology Group, The Glycosciences Laboratory, Northwick Park Hospital Watford Road, Harrow, Middlesex HA1 3UJ, UK 2Mass Spectrometry Group, The Glycosciences Laboratory, Northwick Park Hospital Watford Road, Harrow, Middlesex HA1 3UJ, UK 3Department of Bioregulation, Biomedical Research Center, Osaka University 2-2 Yamada-oka, Suita 565, Osaka, Japan 4Laboratoire de Chimie Organique Multifunctionelle, Universite de Paris Sud Orsay Cedex 91405, France 5Department of Chemistry, Scripps Research Institute La Jolla, CA 92037, USA 6Present address: Department of Expeimental Pathology, UMDS Guy's and St Thomas's Hospitals, University of London London Bridge, London SE1 9RT, UK |
| Abstract: | This communication is concerned with the binding specficityof the leukocyte-adhesion molecule L-selectin (leukocyte homingreceptor) towards structurally defined sulphated oligosaccharidesof the blood group Lea and Lex series, and of the glycolsaminoglycanseries heparin, chondroitin sulphate and keratan sulphate. Therecombinant soluble form of the rat L-selectin (L-selectin-IgGFc chimera) investigated here was shown previously to bind tolipid-linked oligosaccharides 3-O, 4-O and 6-O sulphated atgalactose, such as sulphatides and a mixture of 3-sulphatedLea/Lex type tetrasaccharides isolated from ovarian cystadenoma,as well as to the HNK-1 glycolipid with 3-O sulphated glucuronicacid. In the present study, the L-selectin investigated in bothchromatogram binding and plastic microwell binding experimentsusing neoglycolipids was found to bind to the individual 3-sulphatedLea and Lex sequences (penta-, tetra- and trisaccharides), andwith somewhat lower intensities to their non-fucosylated analogues.Glycosaminoglycan disaccharides of keratan sulphate, heparinand chondroitin sulphate types were also bound by L-selectinin one or both assay systems, leading to the conclusion thatclustered glycosaminoglycan oligosaccharides with 6-O sulphationof N-acetylgalactctosamine, N-acetylglucosamine or glucosamine,4-O sulphation of N-acetylgalactosamine, 2-O sulphation of uronicacid, N-sulphation of glucosamine and, to a lesser extent, thenon-sulphated uronic acid-contahing disaccharides, can supportL-selectin adhesion. As inflammatory chemokines (short-rangestimulators of lymphocyte migration which trigger integrin activation)are known to bind to endothelial glycosaminoglycans, we proposethat the binding of the lymphocyte membrane L-selectin to endothelialglycosaminoglycans may provide a link between the selectin-mediatedand integrin-mediated adhesion systems in leukocyte extravasationcascades. The posibility is also raised that lymphocyte L-selectininteractions with glycosaminoglycans may contribute to pathologiesof glycosaminoglycan-rich tissues, e.g. cartilage loss in rheumatoidarthritis and inflammatory lesions of the cornea. glycosaminoglycans leukocyte adhesion cascades neoglycolipids oligosaccharide presentation sulphated oligosaccharides |
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