Shear-induced von Willebrand factor-mediated platelet surface translocation of the CD40 ligand

Background: Platelets, which can adhere to damaged vascular surfaces and release bioactive substances upon activation, may play important roles in regulating local inflammatory responses. We focused on the surface translocation of CD40 ligand (CD40L) molecules when the platelets are exposed to a high shear stress. Method: Blood specimens were obtained from eight apparently healthy adult donors. The number of CD40L molecules appearing on the surface of platelets after exposure of platelet-rich plasma to a shear rate of 10,800 s^-1 was determined by quantitative flow cytometry. Results: The number of anti-CD40L IgG molecules bound per platelet increased from 15±80/platelet before to 355±122/platelet after exposure of the platelets to a shear rate of 10,800 s^-1 (p<0.01), but not after their exposure to the relatively low shear rate of 1200 s^-1. This shear-induced platelet surface translocation of CD40L, mediated by the von Willebrand factor (VWF)-GP Ibα interaction, was enhanced in the presence of a low concentration of epinephrine (100 nM), which by itself, however, could not cause platelet activation. Our results demonstrate that fluid force induces the appearance of CD40L on the surface of platelets, and also that this phenomenon is enhanced in the presence of a low concentration of epinephrine, corresponding to that released by sympathetic stimulation.