Differential aspects of the glycoprotein Ib-von Willebrand factor axis in human and pig species

Background and Objectives. The role of glycoprotein Ib (GPIb) in platelet a dhesion to subendothelium is well established in human species. However, th e interaction of GPIb and von Willebrand factor (VWF) in a widely used expe rimental model in thrombosis research, that of the pig, has not been dearly elucidated. We investigated the differences between human and pig species in the GPIb/VWF axis in several ways. Design and Methods. Standard aggregometry and perfusion studies with circul ating blood were applied to isolated platelets or to blood reconstituted wi th isolated platelets, VWF and red blood cells from the different species. Platelet aggregation to VWF in the presence of either ristocetin or botroce tin was tested. Results. Human VWF and ristocetin did not agglutinate pig platelets. Howeve r, botrocetin was capable of agglutinating pig platelets. In perfusion stud ies (800 s(-1), 10 min), washed platelets from both species were suspended in albumin solutions containing human VWF (hVWF) or porcine VWF (pVWF) and red blood cells from the corresponding species. Reconstituted blood with hi gh concentrations of pVWF (greater than or equal to 0.25 U/mL) caused sever e thrombocytopenia during the perfusion procedure when added to human plate lets. Nevertheless, lower concentrations (less than or equal to 0.1 U/mL) p romoted the formation of large aggregates. Under our experimental condition s, hVWF poorly supported pig platelet adhesion. Interpretation and Conclusions. In conclusion, pVWF may support human plate let adhesion and even promote aggregation, while hVWF can only partially fa cilitate pig platelet adhesion. Minimal concentrations of pVWF could facili tate the interaction of human platelets with subendothelium, increasing the ir adhesive and aggregating capabilities. Understanding the molecular diffe rences of the GPIb-VWF axis in different species may prove useful for devel oping therapeutic strategies aimed at preventing excessive platelet deposit ion on damaged vascular surfaces (C) 2000, Ferrata Storti Foundation.