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The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P‐ and l ‐selectin function in vivo
Author(s) -
Thorlacius,
Vollmar,
Seyfert,
Vestweber,
Menger
Publication year - 2000
Publication title -
european journal of clinical investigation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.164
H-Index - 107
eISSN - 1365-2362
pISSN - 0014-2972
DOI - 10.1046/j.1365-2362.2000.00704.x
Subject(s) - fucoidan , intravital microscopy , thrombus , in vivo , selectin , p selectin , coagulation , platelet , microcirculation , cremaster muscle , chemistry , immunology , pharmacology , medicine , cell adhesion molecule , biochemistry , platelet activation , biology , polysaccharide , microbiology and biotechnology
Background Adhesion molecules of the selectin family (mainly P‐ and L‐selectin) have been suggested to mediate interactions between platelets, leukocytes and endothelial cells in thrombus formation. The polysaccharide fucoidan has anticoagulative properties, but is also able to bind and block the function of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentially mediated by the inhibition of P‐and/or L‐selectin. Materials and Methods For this purpose, we used intravital microscopy in the mouse cremaster microcirculation in which thrombosis was induced photochemically by light exposure to individual arterioles and venules after intravenous ( i.v .) injection of FITC‐dextran. Results We found that intravenous administration of fucoidan significantly prolonged the time required for complete occlusion in arterioles and venules by almost seven‐ and nine‐fold, respectively. In contrast, treatment with monoclonal antibodies against P‐ and L‐selectin had no effect on the development of microvascular thrombosis. Fucoidan and also the anti‐P‐selectin antibody completely inhibited baseline venular leukocyte rolling in the cremaster muscle, indicating that these treatment regimes abolished P‐selectin function. Importantly, fucoidan and the anti‐P‐selectin antibody had no effect on systemic platelet and leukocyte counts. On the other hand, we found that fucoidan treatment significantly altered coagulation parameters, including prothrombin time (Quick percentage), activated partial thromboplastin time (APTT) and thrombin clotting time (TCT), which may explain the potent in vivo anticoagulative effect of fucoidan observed here. Conclusions Taken together, our novel findings suggest that fucoidan effectively prevents microvascular thrombus formation induced by endothelial damage in arterioles and venules in vivo . This protective effect of fucoidan is not attributable to inhibition of P‐ and L ‐selectin function but may instead be related to the anticoagulative capacity of fucoidan.