Platelets adhere to and translocate on von Willebrand factor presented by endothelium in simulated veins

With the use of intravital microscopy, a new type of platelet-endothelial interaction in mouse mesenteric venules at low shear (80-100 seconds(-1)) is described. Stimulation of these vessels with calcium ionophore A23187, a known secretagogue of Welbel-Palade bodies, induced immediate platelet adhesion (within 15 seconds) and translocation without the formation of aggregates. This stop-and-go process reached a maximum in approximately 1 minute, when approximately 25 000 platelets adhered/mm(2.)s, and then adhesion progressively decreased. This adhesion process was dependent on von Willebrand factor (vWF) and independent of P-selectin. Immunohistologic analysis showed that the venules were not denuded with A23187 treat ment, suggesting that platelets adhered to VWF secreted on the luminal face of the endothelial cells. Histamine treatment induced a similar adhesion phenomenon. Platelet adhesion was not abolished in beta3-deficient mice or when the platelets were treated with inhibitory antibodies to PECAM-1 or PSGL-1, indicating that these molecules are not required for platelet-endothelium interaction at low shear, The adhesion was mediated by platelet glycoprotein lb alpha (GPlb alpha) because the adhesion of murine platelets expressing exclusively the human GPlb alpha could be prevented by a pretreatment with mocarhagin, a snake venom protease that cleaves human GPlb alpha. The results indicate that VWF released from Weibel-Palade bodies can dramatically increase the concentration of platelets along the vessel wall through an interaction with GPlb alpha. It is proposed that this process may rapidly recruit platelets to sites of injury or inflammation in veins. (C) 2000 by The American Society of Hematology.