Mathematical Model of Platelet Intracellular Signaling After Activation by Fucoidan

Abstract

Blood platelets are the cells responsible for prevention of the blood loss. Fucoidan is a brown algae extract that is known to activate platelets via C-type lectin receptor of the second type. On the other hand, different fucoidans are now considered as perspective immunomodulators. Thus, application of fucoidan as a medicinal drug seems to be contradictory. In this work we studied activation of platelets by fucoidan in silico and in vitro. The computational model describes the behavior of the participants of the fucoidan receptor signaling cascade. The model was validated with available experimental data published earlier. In order to confirm the model predictions, the fucoidan-induced activation of platelets was assessed in flow cytometry and aggregometry experiments. The resultant model describes changes in the activity of tyrosine kinases of Syk and Sarc family and subsequent activation of phospholipase Cγ2. One of the main model prediction is a significant increase in the platelet cytosolic calcium level after the activation by fucoidan. This prediction was confirmed in the experiments. Thus, fucoidan, as a true platelet activator, cannot be applied in therapy.