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Biochim Biophys Acta. 2009 Feb;1790(2):141-6. doi: 10.1016/j.bbagen.2008.10.008. Epub 2008 Nov 5.

Affinity of low molecular weight fucoidan for P-selectin triggers its binding to activated human platelets.

Author information

1
Inserm, U698, Cardiovascular Bioengineering, CHU X. Bichat, University Paris 7, Paris, F-75877, France.

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 IC(50) 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 K(D) 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.

PMID:
19026722
DOI:
10.1016/j.bbagen.2008.10.008
[Indexed for MEDLINE]
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