The polysaccharide fucoidan inhibits microvascular thrombus formation independently from P- and L-selectin function in vivo

Background Adhesion molecules of the selectin family (mainly P- and L-selec tin) have been suggested to mediate interactions between platelets, leukocy tes and endothelial cells in thrombus formation. The polysaccharide fucoida n has anticoagulative properties, but is also able to bind and block the fu nction of the selectins. Here, we investigated in vivo (i) if fucoidan can prevent microvascular thrombus formation, and (ii) whether this is potentia lly mediated by the inhibition of P-and/or L-selectin. Materials and Methods For this purpose, we used intravital microscopy in th e mouse cremaster microcirculation in which thrombosis was induced photoche mically by light exposure to individual arterioles and venules after intrav enous (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 venule s by almost seven- and ninefold, respectively In contrast, treatment with m onoclonal antibodies against P- and L selectin had no effect on the develop ment of microvascular thrombosis. Fucoidan and also the anti-P-selectin ant ibody completely inhibited baseline venular leukocyte rolling in the cremas ter muscle, indicating that these treatment regimes abolished P-selectin fu nction. Importantly, fucoidan and the anti-P-selectin antibody had no effec t on systemic platelet and leukocyte counts. On the other hand, we found th at fucoidan treatment significantly altered coagulation parameters, includi ng prothrombin time (Quick percentage), activated partial thromboplastin ti me (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 effect ively prevents microvascular thrombus formation induced by endothelial dama ge in arterioles and venules in vivo. This protective effect of fucoidan is not attributable to inhibition of P- and L-selectin function but may inste ad be related to the anticoagulative capacity of fucoidan.