Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets
- 5 November 2008
- journal article
- research article
- Published by Elsevier BV in Biochimica et Biophysica Acta (BBA) - General Subjects
- Vol. 1790 (2), 141-146
- https://doi.org/10.1016/j.bbagen.2008.10.008
Abstract
Background: P-selectin is an adhesion receptor expressed on activated platelets and endothelial cells. Its natural ligand, P-selectin glycoprotein ligand-1, is expressed on leucocytes and the P-selectin/PSGL-1 interaction is involved in leukocyte rolling. We have compared the interaction of P-selectin with several low molecular weight polysaccharides: fucoidan, heparin and dextran sulfate. Methods: Binding assays were obtained from the interaction of the polysaccharides with Sialyl Lewis X and PSGL-1 based constructs onto microtiter plates coated with P-selectin. SELDI TOF mass spectrometry was performed with anionic chips arrays coated with P-selectin in the absence or in the presence of polysaccharides. Kd were obtained from surface plasmon resonance experiments with immobilized P-selectin constructs, polysaccharides being injected in the mobile phase. Human whole blood flow cytometry experiments were performed with fluorescein isothiocyanate labelled polysaccharides with or without platelets activators. Results: The fucoidan prevented P-selectin binding to Sialyl Lewis X with an IC50 of 20 nM as compared to 400 nM for heparin and < 25000 nM for dextran sulfate. It exhibited the highest affinity for immobilized P-selectin with a KD of 1.2 nM, two orders of magnitude greater than the KD of the other polysaccharides. Mass spectrometry evidenced the formation of a complex between P-selectin and fucoidan. The intensity of the fucoidan binding to platelets was dependent on the level of platelet activation. Competition between fucoidan and an anti P-selectin antibody demonstrated the specificity of the interaction. General significance: Low molecular weight fucoidan is a promising therapeutic agent of natural origin for biomedical applications.Keywords
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