Fucosylated Glycosaminoglycan Oligosaccharide HS14, Derived from Sea Cucumbers, Is a Novel Inhibitor of Platelet Toll-like Receptor 2
(1) Background: Toll-like receptor 2 (TLR2) on platelets is increasingly recognized as a pivotal mediator in infection-induced platelet activation and aggregation, contributing to both inflammatory and thrombotic diseases. Targeting TLR2 on platelets offers a promising therapeutic strategy for infla...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-03-01
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| Series: | Marine Drugs |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1660-3397/23/3/110 |
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| Summary: | (1) Background: Toll-like receptor 2 (TLR2) on platelets is increasingly recognized as a pivotal mediator in infection-induced platelet activation and aggregation, contributing to both inflammatory and thrombotic diseases. Targeting TLR2 on platelets offers a promising therapeutic strategy for inflammatory and thrombotic-related disorders. However, inhibitors targeting platelet TLR2 have not yet been reported. (2) Methods: Platelet aggregation was assessed using a light transmission aggregometer. Platelet activation was evaluated by measuring the release of P-selectin and von Willebrand factor (vWF) via ELISA. Intracellular Ca<sup>2+</sup> mobilization was quantified using Fluo 3-AM fluorescence, recorded by flow cytometry. Static platelet adhesion was visualized under a microscope, and the formation of platelet–granulocyte aggregates in human whole blood was analyzed by flow cytometry. (3) Results: Fucosylated glycosaminoglycan (FG) tetradecasaccharide HS14 inhibited the activation and aggregation of human platelets induced by the synthetic bacterial lipopeptide Pam3CSK4 in a concentration-dependent manner. This inhibitory effect gives rise to significant anti-inflammatory and anti-thrombotic activities, as evidenced by reduced platelet adhesion and decreased platelet–granulocyte aggregates formation in human whole blood. (4) Conclusions: This study is the first to identify FG oligosaccharide HS14 as a promising inhibitor of platelet TLR2/TLR1, demonstrating significant therapeutic potential for inflammatory and thrombotic-related diseases. |
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| ISSN: | 1660-3397 |