Ligand recognition by E-selectin: analysis of conformation and activity of synthetic monomeric and bivalent sialyl Lewis X analogs

DeFrees, Shawn; Gaeta, F. C. A.; Lin, Ying-Chih; Ichikawa, Yoshitaka; Wong, Chi Huey

doi:10.1021/ja00069a083

Cited by 101 publications

(41 citation statements)

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“…Some published reports show that monovalent sLex tetrasaccharide is able to block the P-selectindependent accumulation of granulocytes in models involving lung inflammation or cardiac reperfusion (42,43). In vitro data suggests also that oligosaccharide constructs bearing two sLex groups (divalent sLex structures) are five times better inhibitors of E-selectin-dependent adhesion compared to monovalent sLex (44,45). Although the generation of very complex oligosaccharides has been difficult, enzyme-aided synthesis makes it possible at this time (28).…”

Section: Discussionmentioning

confidence: 99%

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.

Turunen

Majuri

Seppo

et al. 1995

The Journal of Experimental Medicine

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SummaryAcute organ transplant rejection is characterized by a heavy lymphocyte infiltration. We have previously shown that alterations in the graft endothelium lead to increased lymphocyte traffic into the graft. Here, we demonstrate that lymphocytes adhere to the endothelium of rejecting cardiac transplants, but not to the endothelium of syngeneic grafts or normal hearts analyzed with the in vitro Stamper-Woodruff binding assay. Concomitant with the enhanced lymphocyte adhesion, the cardiac endothelium begins to de novo express sialyl Lewis a and sialyl Lewis x (sLea and sLex) epitopes, which have been shown to be sequences of L-selectin counterreceptors. The endothelium of allografts, but not that of syngeneic grafts or normal controls, also reacted with the L-selectin-immunoglobulin G fusion protein, giving further proof of inducible L-selectin counterreceptors. The lymphocyte adhesion to endothelium could be significantly decreased either by treating the iymphocytes with anti-L-selectin antibody HRL-1, or by treating the tissue sections with sialidase or anti-sLea or anti-sLex monoclonal antibodies. Finally, we synthetized enzymatically several members of the sLex family oligosaccharides and analyzed their ability to block lymphocyte adhesion to cardiac endothelium. The monovalent sLex (a tetramer), divalent sLex (a decamer), and tetravalent sLex (a 22-mer) could all significantly reduce lymphocyte binding, but the inhibition by the tetravalent sLex-construct was clearly superior to other members of the sLex family. The crucial control oligosaccharides, sialyl lactosamines lacking fucose but being otherwise similar to the members of sLex family, had no effect on lymphocyte binding.

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Section: Discussionmentioning

confidence: 99%

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.

Turunen

Majuri

Seppo

et al. 1995

The Journal of Experimental Medicine

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“…IC 50 s for the E-selectin antagonist sLe x have been described previously in the literature (12)(13)(14)(15)(16)(17)24). They The sLe a -polymer was incubated with the immobilized E-selectin fusion protein for different times.…”

Section: Sensitivity Of the Assay System Incubation Timementioning

confidence: 99%

An E-Selectin Binding Assay Based on a Polyacrylamide-Type Glycoconjugate

Weitz‐Schmidt

Stokmaier

Scheel

et al. 1996

Analytical Biochemistry

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“…A further difficulty is that if all three selectins recognized the same carbohydrate structure (e.g., SLex), the situation could be impractical because selectin and ligand might appear on the same cell (see Fig. 1 (20,51,62,63,69,70).…”

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confidence: 99%

Selectin ligands.

Varki

1994

Proc. Natl. Acad. Sci. U.S.A.

891

519

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The selectins initiate many critical interactions among blood cells. The volume of information and diversity of opinions on the nature of the biologically relevant ligands for selectins is remarkable. This review analyzes the matter and suggests the hypothesis that at least some of the specificity may involve recognition of "clustered saccharide patches."Five years ago, the cloning of three vascular proteins resulted in identification of the selectin family of cell adhesion molecules (1-9). A shared N-terminal carbohydrate-recognition domain homologous to other Ca2+-dependent (C-type) mammalian lectins (10) strengthened predictions from functional studies (for review, see ref. 1) that the cognate ligands for these receptors would be cell-surface carbohydrates (Fig. 1). Several groups then reported that previously known mammalian oligosaccharides bearing Fuc and sialic acid (Sia) are recognized in a Ca2+-dependent manner by the selectins (11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24). Evidence for the function of selectins in leukocyte trafficking, thrombosis and inflammation, as well as the possibility for therapeutic intervention in reperfusion injury, inflammation, allergy, autoimmunity, and cancer (for review, see refs. 1-9) attracted additional investigators (>500 articles in the last 5 yr).* More recently, specific macromolecular ligands for the selectins have been reported (25-38). Molecular cloning of the polypeptide backbones of some of these molecules indicates that ligand formation is indeed glycosylation-dependent (28,33,34,37,39,40). Some studies suggest that small sialylated, fucosylated oligosaccharides such as sialyl-Lewisx (SLex) and sialyl-Lewisa (SLea) (11,12,20,(22)(23)(24)(41)(42)(43)(44) lectin came from the inhibitory effects of phosphorylated monosaccharides and a phosphorylated yeast mannan on the interaction of lymphocytes with highendothelial venules (HEV) in lymph nodes (1). These studies were inspired by work on a different class of mammalian lectins, the mannose 6-phosphate receptors (52). However, sialidase treatment of lymph node sections abolished lymphocyte-HEV interaction, indicating a critical role for Sia (53). Subsequently, the selective inhibitory properties of various phosphorylated and sulfated saccharides (1) confirmed a lectin-like interaction. It is now evident that the selectin ligands are not themselves phosphorylated (nor always sulfated) and that the inhibitors worked either because of high concentrations or high charge density. In parallel, others (3) described monoclonal antibodies (mAbs) that recognized specific "addressins" involved in lymphocyte trafficking. The peripheral node addressin recognized by mAb MECA-79 (54) is a family of glycoproteins (gps), some of which interact with L-selectin in a Sia-dependent manner (25). Likewise, the mAb HECA-452 recognizes Sia-

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Ligand recognition by E-selectin: analysis of conformation and activity of synthetic monomeric and bivalent sialyl Lewis X analogs

Cited by 101 publications

References 0 publications

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.

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.

An E-Selectin Binding Assay Based on a Polyacrylamide-Type Glycoconjugate

Selectin ligands.

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