Identification of a glycoprotein ligand for E-selectin on mouse myeloid cells.

Inflammatory processes are associated with the rapid migration of dendritic cells (DCs) to regional lymph nodes and depletion of these potent antigen-presenting cells (APCs) from the inflamed tissue. This study examined whether sites of cutaneous inflammation can be repopulated with DCs from a pool of immature DCs circulating in the blood. In adoptive transfer experiments with ex vivo-generated radioactively labeled primary bone marrow-derived DCs injected into mice challenged by an allergic contact dermatitis reaction, immature DCs were actively recruited from the blood to sites of cutaneous inflammation, whereas mature DCs were not. Immature, but not mature, DCs were able to adhere specifically to immobilized recombinant E-and P-selectin under static as well as under flow conditions. P-selectin-dependent adhesion of immature DCs correlates with their higher level of expression of the carbohydrate epitope cutaneous lymphocyte-associated antigen (CLA) and is blocked by a novel inhibitory antibody against mouse P-selectin glycoprotein ligand 1 (PSGL-1). Surprisingly, however, emigration of immature DCs into inflamed skin is retained in the presence of this anti-PSGL-1 antibody and is also normal when immature DCs are generated from fucosyltransferase (Fuc-T) Fuc-TVII-deficient mice. By contrast, emigration of wild-type immature DCs is reduced by adhesion-blocking anti-E-and P-selectin antibodies, and immature DCs generated ex vivo from IntroductionDendritic cells (DCs) are bone marrow-derived leukocytes that are specialized in antigen capture, processing, and presentation to T lymphocytes and are essential for the initiation and modulation of antigen-specific immune responses. 1 DC progenitors as well as more mature DCs are present in small numbers in the blood. 2 They seed nonlymphoid tissues and are primarily localized within epithelia, such as Langerhans cells in the epidermis. 3 On activation these cells undergo phenotypic changes that allow them to migrate from their site of residence to the T-cell areas of regional lymph nodes. 4 The factors that mediate trafficking from the periphery to lymphoid organs are well defined. 5-10 However, not much is known about the immigration of DC precursors to their tissue of residence and only a little information is available about immigration and turnover of DCs in inflamed tissues. Because pathogens, allergens, or contact with CD40L-expressing cells all lead to activation and emigration of resident DCs toward regional lymph nodes, 11 the site of inflammation is rapidly depleted of resident antigen-presenting cells (APCs). Thus, for the maintenance of the antigen-specific immune response, it appears necessary that nonresident APCs be actively recruited to inflamed tissue. The role of the small population of blood DCs is not clear, but it is possible that this cell type forms a "task force" of potent APCs that can rapidly relocate to sites of inflammation. 12 This would result in enhanced local antigen presentation to infiltrating effector T cells and sustained priming o...

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“…30,37,38 The immature DC cell line XS52 was cultured in the presence of GM-CSF and conditioned media from NS47 cells as described previously. 39 …”

Section: Cellsmentioning

confidence: 99%

Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1

Pendl

Robert

Steinert

et al. 2002

Blood

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“…Each of these two ligands requires sLe x for binding, with the difference that ESL-1 requires sLe x on N-glycans (18), whereas PSGL-1 requires it on O-glycans that carry a core-2 branch (21,24). In addition, PSGL-1 requires sulfation of the tyrosine residues within its N terminus for binding to P-selectin (25)(26)(27)(28)(29).…”

mentioning

confidence: 99%

“…We have recently analyzed the selective contribution of Fuc-TVII and Fuc-TIV to the generation of the glycoprotein ligands E-selectin ligand-1 (ESL-1) (18,19) and P-selectin glycoprotein ligand-1 (PSGL-1) (20 -23). Each of these two ligands requires sLe x for binding, with the difference that ESL-1 requires sLe x on N-glycans (18), whereas PSGL-1 requires it on O-glycans that carry a core-2 branch (21,24).…”

mentioning

confidence: 99%

The α(1,3)-Fucosyltransferase Fuc-TIV, but Not Fuc-TVII, Generates Sialyl Lewis X-like Epitopes Preferentially on Glycolipids

Huang

Laskowska²,

Vestweber

et al. 2002

Journal of Biological Chemistry

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Fuc-TIV and Fuc-TVII are the two ␣(1, 3)-fucosyltransferases in myeloid cells responsible for the biosynthesis of sialyl Lewis X (sLe x ), the minimal ligand structure for the selectins. We have compared the ability of Fuc-TIV and Fuc-TVII to generate sLe x -like epitopes in transfected Chinese hamster ovary (CHO)-Pro ؊ 5 cells expressing the P-selectin glycoprotein ligand-1 and the core-2 branching enzyme C2GnT. We found that mouse Fuc-TIV and Fuc-TVII can generate similar levels of cell surface sLe x . Surprisingly however, Fuc-TIV-generated sLe x was resistant to proteinase K and trypsin treatment and could be removed from cells by delipidation with chloroform/methanol, whereas 80 -90% of Fuc-TVIIgenerated sLe x was protease-sensitive, and most of it resistant to delipidation. Despite similar levels of sLe x on the cell surface, Fuc-TVII transfectants adhered to immobilized E-selectin-IgG under static and flow conditions better than Fuc-TIV transfectants. Binding was mainly protease sensitive, indicating that glycoproteins were more efficient ligands than glycolipids. In summary, we conclude that the two fucosyltransferases differ in their in vivo specificity for acceptor substrates with Fuc-TVII generating sLe x preferentially on glycoproteins, whereas most of the Fuc-TIV-generated sLe x is found on glycolipids. Interestingly, the non-catalytic portion of Fuc-TIV in a Fuc-TIV/VII chimeric enzyme mediated the specificity for glycolipid substrates.The three known selectins, L-, E-, and P-selectin are cell adhesion molecules that initiate interactions between leukocytes and endothelial cells during leukocyte extravasation (1). The minimal ligand structure for all three selectins is the tetrasaccharide sialyl Lewis X (sLe x ). 1

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“…In the case of P-and L-selectin, glycoprotein ligands have been elucidated that possess multiple O-linked oligosaccharides terminating in SLe x or sulfo-Le x glycans (33)(34)(35). Alternatively, a proposed ligand for E-selectin (ESL-1) loses its binding activity upon treatment with N-glycosidase F, implicating the involvement of N-linked oligosaccharides as ligands for E-selectin (18). However, it remains unclear how the ligand valency for E-, P-, and L-selectin relates to the oligomeric state of the receptors on the cell Table I.…”

Section: Discussionmentioning

confidence: 99%

“…Confocal laser scanning microscopy determined that E-selectin clusters on activated human umbilical venule endothelial cells in response to binding to HL-60 cells (17). A proposed natural ligand for E-selectin (ESL-1) requires its N-glycosylation for high affinity binding to the lectin (18,19). Pooled SLe x N-linked glycopeptides have been used to block E-selectin-mediated inflammation in vivo (20).…”

mentioning

confidence: 99%

In Vivo Ligand Specificity of E-selectin Binding to Multivalent Sialyl Lewisx N-linked Oligosaccharides

Thomas

Yang

Rice

1999

Journal of Biological Chemistry

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The in vivo specificity for E-selectin binding to a panel of N-linked oligosaccharides containing a clustered array of one to four sialyl Lewis x (SLe x ; NeuAc␣2-3Gal[Fuc␣1-3]␤1-4GlcNAc) determinants was studied in mice. Following intraperitoneal dosing with lipopolysaccharide, radioiodinated tyrosinamide N-linked oligosaccharides were dosed i.v. and analyzed for their pharmacokinetics and biodistribution. Specific targeting was determined from the degree of SLe x oligosaccharide targeting relative to a sialyl oligosaccharide control. Oligosaccharides targeted the kidney with the greatest selectivity after a 4-h induction period following lipopolysaccharide dosing. Unique pharmacokinetic profiles were identified for SLe x biantennary and triantennary oligosaccharides but not for monovalent and tetraantennary SLe x oligosaccharides or sialyl oligosaccharide controls. Biodistribution studies established that both SLe x biantennary and triantennary oligosaccharides distributed to the kidney with 2-3-fold selectivity over sialyl oligosaccharide controls, whereas monovalent and tetraantennary SLe x oligosaccharides failed to mediate specific kidney targeting. Simultaneous dosing of SLe x biantennary or triantennary oligosaccharide with a mouse anti-E-selectin monoclonal antibody blocked kidney targeting, whereas co-administration with anti-P-selectin monoclonal antibody did not significantly block kidney targeting. The results suggest that SLe x biantennary and triantennary are N-linked oligosaccharide ligands for E-selectin and implicate E-selectin as a bivalent receptor in the murine kidney endothelium.

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Identification of a glycoprotein ligand for E-selectin on mouse myeloid cells.

Cited by 179 publications

References 49 publications

Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1

Immature mouse dendritic cells enter inflamed tissue, a process that requires E- and P-selectin, but not P-selectin glycoprotein ligand 1

The α(1,3)-Fucosyltransferase Fuc-TIV, but Not Fuc-TVII, Generates Sialyl Lewis X-like Epitopes Preferentially on Glycolipids

In Vivo Ligand Specificity of E-selectin Binding to Multivalent Sialyl Lewisx N-linked Oligosaccharides

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