scholarly journals CD62 and endothelial cell-leukocyte adhesion molecule 1 (ELAM-1) recognize the same carbohydrate ligand, sialyl-Lewis x.

1991 ◽  
Vol 88 (14) ◽  
pp. 6224-6228 ◽  
Author(s):  
M. J. Polley ◽  
M. L. Phillips ◽  
E. Wayner ◽  
E. Nudelman ◽  
A. K. Singhal ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Leukocyte Adhesion Molecule ◽  
Sialyl Lewis ◽  
Carbohydrate Ligand

scholarly journals The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide

1992 ◽  
Vol 117 (4) ◽  
pp. 895-902 ◽  
Author(s):  
C Foxall ◽  
SR Watson ◽  
D Dowbenko ◽  
C Fennie ◽  
LA Lasky ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Structural Features ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Leukocyte Adhesion Molecule ◽  
Lectin Domain ◽  
Calcium Dependent ◽  
Carbohydrate Epitope ◽  
Sialyl Lewis

The selectins (lectin-EGF-complement binding-cell adhesion molecules [LEC-CAMs]) are a family of mammalian receptors implicated in the initial interactions between leukocytes and vascular endothelia, leading to lymphocyte homing, platelet binding, and neutrophil extravasation. The three known selectins, L-selectin (leukocyte adhesion molecule-1 [LECAM-1]), E-selectin (endothelial-leukocyte adhesion molecule-1 [ELAM-1]), and P-selectin (GMP-140) share structural features that include a calcium-dependent lectin domain. The sialyl Lewis(x) carbohydrate epitope has been reported as a ligand for both E- and P-selectins. Although L-selectin has been demonstrated to bind to carbohydrates, structural features of potential mammalian carbohydrate ligand(s) have not been well defined. Using an ELISA developed with a sialyl Lewis(x)-containing glycolipid and an E-selectin-IgG chimera, we have demonstrated the direct binding of the L-selectin-IgG chimera to sialyl Lewis(x). This recognition was calcium dependent, and could be blocked by Mel-14 antibody but not by other antibodies. Recognition was confirmed by the ability of cells expressing the native L-selectin to adhere to immobilized sialyl Lewis(x). These data suggest that the sialyl Lewis(x) oligosaccharide may form the basis of a recognition domain common to all three selectins.

Glycan engineering using synthetic ManNAc analogues enhances sialyl-Lewis-X expression and adhesion of leukocytes

2021 ◽  
Author(s):  
Anam Tasneem ◽  
Shubham Parashar ◽  
Tanya Jain ◽  
Simran Aittan ◽  
Jyoti Rautela ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Inflammatory Diseases ◽  
Leukocyte Adhesion ◽  
Fold Increase ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Sialyl Lewis ◽  
Acute Myeloid Leukemia Cells ◽  
Coated Surfaces ◽  
Cell Cell

Cell surface glycans, depending on their structures and dynamic modifications, act as the first point of contact and regulate cell-cell, cell-matrix, and cell-pathogen interactions. Particularly, the sialyl-Lewis-X (sLeX, CD15s) tetrasaccharide epitope, expressed on both glycoproteins and gangliosides, participates in leukocyte extravasation via interactions with selectins expressed on endothelial cells, lymphocytes, and platelets (CD62-E/L/P). Neutrophils carrying sLeX epitopes are thought to be responsible for chronic inflammatory diseases resulting in plaque formation and atherosclerosis. Intense efforts have been devoted to the development of sLeX mimetics for inhibition of cell adhesion. On the other hand, dysregulated expression of sLeX and poor extravasation are the major underlying causes of leukocyte adhesion deficiency-II (LAD-II) disorders that result in frequent infections and poor immune response. We hypothesized that metabolic processing of peracetyl N-(cycloalkyl)acyl-D-mannosamine derivatives, through the sialic acid pathway, might result in the expression of sialoglycans with altered hydrophobicity which in-turn could modulate their binding to endogenous lectins, including selectins. Herein, we show that treatment of HL-60 (human acute myeloid leukemia) cells with peracetyl N-cyclobutanoyl-D-mannosamine (Ac4ManNCb), at 50 microM for 48 h, resulted in a robust three to four fold increase in the binding of anti-sLeX (CSLEX1) antibody and enhanced cell adhesion to E-selectin coated surfaces; while the corresponding straight-chain analogue, peracetyl N-pentanoyl-D-mannosamine (Ac4ManNPent), and peracetyl N-cyclopropanoyl-D-mannosamine (Ac4ManNCp) both resulted in 2.0-2.5fold increase compared to controls. The ability to enhance sLeX expression using small molecules has the potential to provide novel opportunities to address challenges in the treatment of immune deficiency disorders.

scholarly journals The cutaneous lymphocyte antigen is a skin lymphocyte homing receptor for the vascular lectin endothelial cell-leukocyte adhesion molecule 1.

1991 ◽  
Vol 174 (6) ◽  
pp. 1461-1466 ◽  
Author(s):  
E L Berg ◽  
T Yoshino ◽  
L S Rott ◽  
M K Robinson ◽  
R A Warnock ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cell ◽  
Adhesion Molecule ◽  
Leukocyte Adhesion ◽  
Lymphocyte Homing ◽  
Neuraminidase Treatment ◽  
Leukocyte Adhesion Molecule ◽  
Homing Receptor ◽  
Lymphocyte Antigen ◽  
Cutaneous Lymphocyte Antigen

A skin-associated population of memory T lymphocytes, defined by expression of the cutaneous lymphocyte antigen (CLA), binds selectively and avidly to the vascular lectin endothelial cell-leukocyte adhesion molecule 1 (ELAM-1), an interaction that may be involved in targeting of CLA+ T cells to cutaneous sites of chronic inflammation. Here we present evidence that CLA itself is the (or a) lymphocyte homing receptor for ELAM-1. Antigen isolated with anti-CLA monoclonal antibody HECA-452 from human tonsillar lysates avidly binds ELAM-1 transfected mouse cells. Anti-CLA antibody blocks T lymphocyte binding to ELAM-1 transfectants. HECA-452 and ELAM-1 binding to lymphocytes or to isolated tonsillar HECA-452 antigen is abrogated by neuraminidase treatment implying a prominent role for sialic acid in CLA structure and function. The dominant form of CLA on T cells is immunologically distinct from the major neutrophil ELAM-1 ligand, the sialyl Lewis x (sLex) antigen (NeuAc alpha 2-3Gal beta 1-4[Fuc alpha 1-3]GlcNAc), which is absent, weakly expressed, or masked on T cells. However, neuraminidase treatment of CLA+ T cells, but not of CLA- T cells, reveals Lewis x (CD15) structures. In combination with the known requirement for terminal NeuAc alpha 2-3Gal and fucose residues attached to N-acetylglucosamine for ELAM-1 and HECA-452 binding, this finding suggests that CLA may comprise an additionally sialylated or otherwise modified form of sLex. The identification of a lymphocyte homing receptor for skin may permit novel approaches to the diagnosis and therapy of cutaneous and inflammatory disorders.

scholarly journals Fluorinated per-acetylated GalNAc metabolically alters glycan structures on leukocyte PSGL-1 and reduces cell binding to selectins

Blood ◽  
2010 ◽  
Vol 115 (6) ◽  
pp. 1303-1312 ◽  
Author(s):  
Dhananjay D. Marathe ◽  
Alexander Buffone ◽  
E. V. Chandrasekaran ◽  
Jun Xue ◽  
Robert D. Locke ◽  
...  
Keyword(s):  
Inflammatory Diseases ◽  
Leukocyte Adhesion ◽  
Human Leukocyte ◽  
Sialyl Lewis X ◽  
Metabolic Inhibitor ◽  
Growth Media ◽  
Cell Binding ◽  
Lewis X ◽  
Sialyl Lewis

Abstract Novel strategies to control the binding of adhesion molecules belonging to the selectin family are required for the treatment of inflammatory diseases. We tested the possibility that synthetic monosaccharide analogs can compete with naturally occurring sugars to alter the O-glycan content on human leukocyte cell surface selectin-ligand, P-selectin glycoprotein ligand-1 (PSGL-1). Resulting reduction in the sialyl Lewis-X–bearing epitopes on this ligand may reduce cell adhesion. Consistent with this hypothesis, 50μM per-acetylated 4F-GalNAc added to the growth media of promyelocytic HL-60 cells reduced the expression of the cutaneous lymphocyte associated-antigen (HECA-452 epitope) by 82% within 2 cell doubling cycles. Cell binding to all 3 selectins (L-, E-, and P-selectin) was reduced in vitro. 4F-GalNAc was metabolically incorporated into PSGL-1, and this was accompanied by an approximately 20% reduction in PSGL-1 glycan content. A 70% to 85% reduction in HECA-452 binding epitope and N-acetyl lactosamine content in PSGL-1 was also noted on 4F-GalNAc addition. Intravenous 4F-GalNAc infusion reduced leukocyte migration to the peritoneum in a murine model of thioglycolate-induced peritonitis. Thus, the compound has pharmacologic activity. Overall, the data suggest that 4F-GalNAc may be applied as a metabolic inhibitor to reduce O-linked glycosylation, sialyl Lewis-X formation, and leukocyte adhesion via the selectins.

scholarly journals The selectin GMP-140 binds to sialylated, fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells.

1991 ◽  
Vol 115 (2) ◽  
pp. 557-564 ◽  
Author(s):  
Q Zhou ◽  
K L Moore ◽  
D F Smith ◽  
A Varki ◽  
R P McEver ◽  
...  
Keyword(s):  
Leukocyte Adhesion ◽  
Structural Features ◽  
Sialyl Lewis X ◽  
Lewis X ◽  
Ligand Interaction ◽  
Sialyl Lewis ◽  
Activated Platelets ◽  
Granule Membrane ◽  
Myeloid Leukocytes ◽  
Endothelial Leukocyte Adhesion Molecule

Granule membrane protein-140 (GMP-140) is an inducible receptor for myeloid leukocytes on activated platelets and endothelium. Like other selectins, GMP-140 recognizes specific oligosaccharide ligands. However, prior data on the nature of these ligands are contradictory. We investigated the structural features required for ligand interaction with GMP-140 using purified GMP-140, cells naturally expressing specific oligosaccharides, and cells expressing cloned glycosyltransferases. Like the related selectin endothelial leukocyte adhesion molecule-1 (ELAM-1), GMP-140 recognizes alpha(2-3)sialylated, alpha(1-3)fucosylated lactosaminoglycans on both myeloid and nonmyeloid cells, including the sequence Neu5Ac alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNac beta-R (sialyl Lewis x). Recognition requires sialic acid, because cells expressing large amounts of Lewis x, but not sialyl Lewis x, do not interact with GMP-140. Although sialyl Lewis x is expressed by both myeloid HL-60 cells and CHO cells transfected with an alpha 1-3/4 fucosyltransferase, GMP-140 binds with significantly higher affinity to HL-60 cells. Thus, the sialyl Lewis x tetrasaccharide may require additional structural modifications or specific presentations in order for leukocytes in flowing blood to interact rapidly and with high affinity to GMP-140 on activated platelets or endothelium.

Thrombin receptor peptide-mediated leukocyte rolling in rat mesenteric venules: roles of P-selectin and sialyl Lewis X

1994 ◽  
Vol 267 (3) ◽  
pp. H1049-H1053 ◽  
Author(s):  
B. J. Zimmerman ◽  
J. C. Paulson ◽  
T. S. Arrhenius ◽  
F. C. Gaeta ◽  
D. N. Granger
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Sialyl Lewis X ◽  
Thrombin Receptor ◽  
Leukocyte Rolling ◽  
Lewis X ◽  
Sialyl Lewis ◽  
Rat Mesentery ◽  
Rolling Leukocytes ◽  
Endothelial Cell Adhesion

Neutrophil adhesion to monolayers of cultured endothelial cells is enhanced, via a P-selectin-mediated mechanism, by a 14-amino acid peptide fragment (TRP-14) of the thrombin receptor. The objective of this study was to determine whether TRP-14 promotes P-selectin-mediated sialyl Lewis X-dependent leukocyte rolling in postcapillary venules. Superfusion of the rat mesentery with TRP-14 for 30 min resulted in the recruitment of rolling leukocytes and a concomitant reduction in leukocyte rolling velocity. Analogues of TRP-14 were largely ineffective in promoting leukocyte-endothelial cell adhesion. Treatment with either a monoclonal antibody directed against rat P-selectin or soluble sialyl Lewis X oligosaccharide (the carbohydrate ligand to P-selectin found on leukocytes) significantly attenuated the TRP-14-induced recruitment of rolling leukocytes. However, no effect was observed with a nonbinding antibody or a control fucose-deficient oligosaccharide. These results indicate that TRP-14 elicits the recruitment of rolling leukocytes in postcapillary venules via a P-selectin-dependent mechanism. The results also support the view that sialyl Lewis X participates in P-selectin-mediated leukocyte-endothelial cell adhesion.

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