E- and P-Selectin: Differences, Similarities and Implications for the Design of P-Selectin Antagonists

Binder, Florian; Ernst, Beat

doi:10.2533/chimia.2011.210

Cited by 20 publications

(24 citation statements)

References 39 publications

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“…As an important member of selectins, P-selectin is a sign of endothelial cells' and platelets' activation, playing an essential role in the occurrence of a variety of inflammatory diseases [19,20]. It is currently considered that P-selectin and its mediated endothelial injury and platelet aggregation are involved in the development of DN [21].…”

Section: Discussionmentioning

confidence: 99%

Effects of Magnoline on P-Selectin's Expression in Diabetic Rats and its Reno-Protection

Zhou

Wang

Hao

et al. 2013

Kidney Blood Press Res

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Background and Objective: Magnoline is an active ingredient of magnolia fargesii with anti-inflammatory and anti-platelet effects. The objective is to explore the renoprotection of magnoline in diabetic rats and its effects on P-selectin. Methods: Thirty-six rats were randomized into 4 groups—normal control group (C), diabetic group (D), small-dose magnoline treatment group (M1) and large-dose magnoline treatment group (M2) (n=9 in each group). Streptozotocin was selected to construct diabetic rat model, and group M1 and group M2 were treated with magnoline 0.5mg/Kg.d and 2mg/Kg.d respectively. Urinary albumin excretion rate, renal function, levels of P-selectin and TGF-β1 were observed after 16 weeks. Results: Levels of albuminuria and serum creatinine of group M1 (1078.9 ± 77.3μg/24h, 29.7 ± 3.9μmol/L) and M2 (852.9 ± 80.1μg/24h, 30.9 ± 2.9μmol/L) were lower than group D (1572.8 ± 176.2μg/24h, 39.4 ± 4.1μmol/L) (P <0.05). Serum levels of P-selectin in group M1 and M2 were lower than group D (P <0.05). The renal expression of P-selectin and TGF-β1 in group M1 and M2 were significantly attenuated respectively. Conclusions: Magnoline has reno-protective effects on diabetic rats which may be related to the inhibition of P-selectin.

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Section: Discussionmentioning

confidence: 99%

Effects of Magnoline on P-Selectin's Expression in Diabetic Rats and its Reno-Protection

Zhou

Wang

Hao

et al. 2013

Kidney Blood Press Res

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“…These events are driven by the cell surface levels of PSGL-1 on leukocytes, and of P-selectin on the surface of activated circulating platelets, as evidenced by the fact that administration of either anti-PSGL-1 or anti-P-selectin antibodies almost entirely abrogates pulmonary recruitment of eosinophils, neutrophils and T cells in mice ( Pitchford et al 2005 , 2008 ; Kornerup et al 2010 ). As a critical step in the cascade of events required for the recruitment of inflammatory cells, the P-selectin/PSGL-1 interaction therefore represents a promising target for therapeutic intervention, e.g., in chronic inflammatory conditions such as asthma and COPD ( Binder and Ernst 2011 ).…”

Section: Introductionmentioning

confidence: 99%

“…There are two main pharmacological anti-selectin strategies: the direct disruption of the selectin/selectin-ligand interaction with a selectin antagonist ( Binder and Ernst 2011 ), and the reduction of cell surface levels of functional PSGL-1, the main selectin ligand. Structurally, PSGL-1 is a homodimer composed of two heavily O -glycosylated 120-kDa monomers ( Wilkins et al 1996 , reviewed in Moore 1998 ).…”

Section: Introductionmentioning

confidence: 99%

Base-modified UDP-sugars reduce cell surface levels of P-selectin glycoprotein 1 (PSGL-1) on IL-1β-stimulated human monocytes

et al. 2016

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P-selectin glycoprotein ligand-1 (PSGL-1, CD162) is a cell-surface glycoprotein that is expressed, either constitutively or inducibly, on all myeloid and lymphoid cell lineages. PSGL-1 is implicated in cell–cell interactions between platelets, leukocytes and endothelial cells, and a key mediator of inflammatory cell recruitment and transmigration into tissues. Here, we have investigated the effects of the β-1,4-galactosyltransferase inhibitor 5-(5-formylthien-2-yl) UDP-Gal (5-FT UDP-Gal, compound 1) and two close derivatives on the cell surface levels of PSGL-1 on human peripheral blood mononuclear cells (hPBMCs). PSGL-1 levels were studied both under basal conditions, and upon stimulation of hPBMCs with interleukin-1β (IL-1β). Between 1 and 24 hours after IL-1β stimulation, we observed initial PSGL-1 shedding, followed by an increase in PSGL-1 levels on the cell surface, with a maximal window between IL-1β-induced and basal levels after 72 h. All three inhibitors reduce PSGL-1 levels on IL-1β-stimulated cells in a concentration-dependent manner, but show no such effect in resting cells. Compound 1 also affects the cell surface levels of adhesion molecule CD11b in IL-1β-stimulated hPBMCs, but not of glycoproteins CD14 and CCR2. This activity profile may be linked to the inhibition of global Sialyl Lewis presentation on hPBMCs by compound 1, which we have also observed. Although this mechanistic explanation remains hypothetical at present, our results show, for the first time, that small molecules can discriminate between IL-1β-induced and basal levels of cell surface PSGL-1. These findings open new avenues for intervention with PSGL-1 presentation on the cell surface of primed hPBMCs and may have implications for anti-inflammatory drug development.

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“…Progresses in the development of glycomimetics targeted against sugar binding proteins (lectins) have been reviewed recently [8, 13,14]. Additional recent examples include glycomimetic antagonists of selectins, [18] [22]. In the present review, after describing some general characteristics of glycomimetic structures and of their design and to recapitulate some points about medically relevant lectins, we will describe some examples of design synthesis and characterization of monovalent and multivalent antagonists of the dendritic cell C-lectin DC-SIGN (dendritic cell-specific intercellular adhesion molecule 3-grabbing non integrin), [23] implicated in many infection processes.…”

Section: Introductionmentioning

confidence: 99%

Editorial [Hot Topic: Carbohydrate Mimetics as Potential Drug Candidates]

Soengas¹

2012

MRMC

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Mimics of oligosaccharides capable of interfering with lectin activity are currently being pursued by a number of groups in an effort to produce tools for glycobiology and to design antagonists of medically relevant lectins. The field is reviewed in this chapter. After a brief overview of the state of the art, examples from our and others' studies on the dendritic cell receptor DC-SIGN are illustrated.

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E- and P-Selectin: Differences, Similarities and Implications for the Design of P-Selectin Antagonists

Cited by 20 publications

References 39 publications

Effects of Magnoline on P-Selectin's Expression in Diabetic Rats and its Reno-Protection

Effects of Magnoline on P-Selectin's Expression in Diabetic Rats and its Reno-Protection

Base-modified UDP-sugars reduce cell surface levels of P-selectin glycoprotein 1 (PSGL-1) on IL-1β-stimulated human monocytes

Editorial [Hot Topic: Carbohydrate Mimetics as Potential Drug Candidates]

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