Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2)

Manne, B. K., Getz, T. M., Hughes, C. E. ORCID: https://orcid.org/0000-0002-9790-5820, Alshehri, O., Dangelmaier, C., Naik, U. P., Watson, S. P. and Kunapuli, S. P. (2013) Fucoidan is a novel platelet agonist for the C-type lectin-like receptor 2 (CLEC-2). The Journal of Biological Chemistry, 288 (11). pp. 7717-7726. ISSN 1083-351X doi: 10.1074/jbc.M112.424473

Abstract/Summary

Fucoidan, a sulfated polysaccharide from Fucus vesiculosus, decreases bleeding time and clotting time in hemophilia, possibly through inhibition of tissue factor pathway inhibitor. However, its effect on platelets and the receptor by which fucoidan induces cellular processes has not been elucidated. In this study, we demonstrate that fucoidan induces platelet activation in a concentration-dependent manner. Fucoidan-induced platelet activation was completely abolished by the pan-Src family kinase (SFK) inhibitor, PP2, or when Syk is inhibited. PP2 abolished phosphorylations of Syk and Phospholipase C-γ2. Fucoidan-induced platelet activation had a lag phase, which is reminiscent of platelet activation by collagen and CLEC-2 receptor agonists. Platelet activation by fucoidan was only slightly inhibited in FcRγ-chain null mice, indicating that fucoidan was not acting primarily through GPVI receptor. On the other hand, fucoidan-induced platelet activation was inhibited in platelet-specific CLEC-2 knock-out murine platelets revealing CLEC-2 as a physiological target of fucoidan. Thus, our data show fucoidan as a novel CLEC-2 receptor agonist that activates platelets through a SFK-dependent signaling pathway. Furthermore, the efficacy of fucoidan in hemophilia raises the possibility that decreased bleeding times could be achieved through activation of platelets.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/44570
Identification Number/DOI	10.1074/jbc.M112.424473
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences
Publisher	American Society for Biochemistry and Molecular Biology
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