Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of sialic acid

Shodai, Tomonori; Suzuki, Junsuke; Kudo, Sanae; Itoh, Saotomo; Tomita, Masaki; Fujita, Shuji; Shimazu, Hajime; Tsuji, Tsutomu

doi:10.1016/j.bbrc.2003.10.188

Cited by 18 publications

(11 citation statements)

References 46 publications

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“…We do not rule out the possibility that NMSO3 may mediate an inhibitory effect on viruses other than through negative charge. NMSO3 has been shown to act as a specific inhibitor for P-selectin, a carbohydrate-binding cell adhesion molecule (45). The inhibitory effect of NMSO3 on pseudotype plaque formation appeared to interfere with virus attachment to the cells, and this effect was significantly higher (Ͼ20-fold) on the VSVts045 backbone used for the generation of the pseudotypes than on the E1-G/E2-G pseudotype.…”

Section: Resultsmentioning

confidence: 99%

Coexpression of Hepatitis C Virus E1 and E2 Chimeric Envelope Glycoproteins Displays Separable Ligand Sensitivity and Increases Pseudotype Infectious Titer

Meyer¹,

Beyene²,

Bowlin

et al. 2004

J Virol

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We have previously reported that a pseudotype virus generated by reconstitution of hepatitis C virus (HCV) chimeric envelope glycoprotein E1-G or E2-G on the surface of a temperature-sensitive mutant of vesicular stomatitis virus (VSVts045) interacts independently with mammalian cells to initiate infection. Here, we examined whether coexpression of both of the envelope glycoproteins on pseudotype particles would augment virus infectivity and/or alter the functional properties of the individual subunits. Stable transfectants of baby hamster kidney (BHK) epithelial cells expressing either one or both of the chimeric envelope glycoproteins of HCV on the cell surface were generated. The infectious titer of the VSV pseudotype, derived from a stable cell line incorporating both of the chimeric glycoproteins of HCV, was ϳ4-to 5-fold higher than that of a pseudotype bearing E1-G alone or ϳ25-to 30-fold higher than that of E2-G alone when assayed with a number of mammalian cell lines. Further studies suggested that that the E1-G/E2-G or E2-G pseudotype was more sensitive to the inhibitory effect of heparin than the E1-G pseudotype. Treatment of the E1-G/E2-G pseudotype with a negatively charged sulfated sialyl lipid (NMSO3) displayed a ϳ4-fold-higher sensitivity to neutralization than pseudotypes with either of the two individual glycoproteins. In contrast, VSVts045, used as a backbone for the generation of pseudotypes, displayed at least 20-fold-higher sensitivity to NMSO3-mediated inhibition of virus plaque formation. The effect of low-density lipoprotein on the E1-G pseudotype was greater than that apparent for the E1-G/E2-G pseudotype. The treatment of cells with monoclonal antibodies to CD81 displayed an inhibitory effect upon the pseudotype with E1-G/E2-G or with E2-G alone. Taken together, our results indicate that the HCV E1 and E2 glycoproteins have separable functional properties and that the presence of these two envelope glycoproteins on VSV/HCV pseudotype particles increases infectious titer.Hepatitis C virus (HCV) is a major causative agent of parentally transmitted hepatitis (12) and is associated with liver cirrhosis and hepatocellular carcinoma (2). Approximately 25% of infected individuals appear to clear viremia without therapeutic intervention (3,30), and the mechanism leading to this natural resolution of HCV infection is not completely understood. The majority of HCV-infected individuals do not resolve infection and may eventually develop chronic hepatitis. The study of HCV is challenging due to its inefficient replication in cell culture and the lack of a small-animal model.The HCV genome is a linear, positive-sense, single-stranded RNA molecule of ϳ9,500 nucleotides. It encodes a polyprotein precursor of ϳ3,000 amino acids (13) which is cleaved by both host and viral proteases to generate several distinct polypeptides (24, 26). The structural proteins, core, E1, and E2, of HCV physically interact and may have a role in virus assembly (8,15,34). The glycosylated polypeptides (E1 and E2) are most li...

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Section: Resultsmentioning

confidence: 99%

Coexpression of Hepatitis C Virus E1 and E2 Chimeric Envelope Glycoproteins Displays Separable Ligand Sensitivity and Increases Pseudotype Infectious Titer

Meyer¹,

Beyene²,

Bowlin

et al. 2004

J Virol

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“…The adhesion of HL-60 cells to CHO-P cells was assayed as described previously [19]. HL-60 cells were labeled with 2 μM calcein AM, at 37ºC for 30 min.…”

Section: Static Adhesion Assaymentioning

confidence: 99%

Sulfochitosan inhibits P-selectin-mediated HL-60 leukocyte adhesion under flow conditions

Huang

Wang

Liu

et al. 2013

Cellular and Molecular Biology Letters

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Excessive trafficking of leukocytes can lead to serious tissue injury. Here, four regioselectively sulfated chitosans were assessed as inhibitors of HL-60 leukocyte binding to P-selectin, by investigating their effect on leukocyte adhesion to CHO cells expressing human P-selectin under static and flow conditions. The results show that the sulfochitosans exhibit inhibitory activity in this general order: heparin > N-sulfated/6-O-sulfated chitosan ≥ 3-O,6-O-sulfated chitosan > 6-O-sulfated chitosan ≫ N-sulfated chitosan. This suggests that the sulfation of the double site in chitosan is essential for efficient inhibition of P-selectin-mediated HL-60 leukocyte adhesion and that such sulfochitosans may have potential as therapeutic agents against inflammatory disease.

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“…Many studies have shown that mimics of SLe X , oligosaccharides, and sulfated polysaccharides such as heparin, heparan sulfate, dextran sulfate, and fucoidan or some of their derivatives were able to interact with P-selectin (12,13,30). Among them, fucoidans are a family of polysaccharides extracted mainly from brown algae and containing a substantial percentage of L-fucose and ester sulfate.…”

Section: P-selectin-targeted Imaging Agentsmentioning

confidence: 99%

“…These agents were built either on anti-P-selectin antibodies or on synthetic mimics of sialyl Lewis X (SLe X ), which is the natural ligand of P-selectin (12,13). Although effective, the cost of synthesis of these agents and the risk of immunogenicity of antibodies preclude a potential translation to clinical use.…”

mentioning

confidence: 99%

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

Rouzet

Bachelet-Violette

Alsac³

et al. 2011

J Nucl Med

115

107

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P-selectin expression is involved in the pathophysiology of biologically active arterial thrombus and endothelial activation after a transient ischemic event. Fucoidan is a polysaccharidic ligand of P-selectin, with a nanomolar affinity. In the present study, we propose a new approach of P-selectin molecular imaging based on radiolabeled fucoidan. Methods: Two kinds of experimental models were selected to evaluate the ability of radiolabeled fucoidan to detect P-selectin expression: plateletrich arterial thrombi (vegetations of infective endocarditis and arterial mural thrombus) and myocardial ischemia-reperfusion. These 2 settings were chosen because they were clinically relevant, and both were associated with an important overexpression of platelet and endothelial P-selectin, respectively. Results: 99m Tc-fucoidan SPECT was able to detect the presence of platelet-rich arterial thrombi in all animals, with a median target-to-background ratio of 5.2 in vegetations of endocarditis and 3.6 in mural aneurysmal thrombus, and to detect a persistent endothelial activation at 2 h after reperfusion. In this latter model, the magnitude of the signal was correlated with the extent of myocardium that underwent transient ischemia. The sensitivity of selectivity of the uptake and retention of 99m Tc-fucoidan in both settings was excellent. Conclusion: This study supports 99m Tc-fucoidan as a relevant imaging agent for in vivo detection of biologic activities associated with P-selectin overexpression, such as arterial thrombus and ischemic memory. Given the reported wide availability at a low cost, and its low toxicity, fucoidan seems to overcome some of the limitations of previous P-selectin-targeted imaging agents.Key Words: P-selectin; fucoidan; thrombus; ischemia; imaging J Nucl Med 2011; 52:1433-1440 DOI: 10.2967/jnumed.110.085852 P-sel ectin is an adhesion molecule expressed at the surface of endothelial cells and platelets on activation. It mediates leukocyte rolling on activated endothelium (1) and leukocyte trapping on platelet aggregates (2), through the interaction with its counterreceptor P-selectin glycoprotein ligand 1. In the cardiovascular field, P-selectin expression is involved in the pathophysiology of 2 settings of prominent clinical relevance: the renewal and growth of biologically active (at risk) arterial thrombus (2) and endothelial activation after an acute transient myocardial ischemic event referred to as ischemic memory (3). Activated platelets expose granular P-selectin on their membrane surface, and myocardial injury is associated with activation of endothelial cells resulting in Weibel-Palade bodies exocytosis and overexpression of adhesion molecules (1,4), which persists after ischemia has resolved. Therefore, P-selectin promotes platelet, endothelium, and leukocyte interactions, whatever the cardiovascular events, representing an important molecular target in acute and in chronic cardiovascular diseases.Consequently, many efforts have been made to develop imaging agents targeting P-selectin (5...

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Inhibition of P-selectin-mediated cell adhesion by a sulfated derivative of sialic acid

Cited by 18 publications

References 46 publications

Coexpression of Hepatitis C Virus E1 and E2 Chimeric Envelope Glycoproteins Displays Separable Ligand Sensitivity and Increases Pseudotype Infectious Titer

Coexpression of Hepatitis C Virus E1 and E2 Chimeric Envelope Glycoproteins Displays Separable Ligand Sensitivity and Increases Pseudotype Infectious Titer

Sulfochitosan inhibits P-selectin-mediated HL-60 leukocyte adhesion under flow conditions

Radiolabeled Fucoidan as a P-Selectin Targeting Agent for In Vivo Imaging of Platelet-Rich Thrombus and Endothelial Activation

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