Two novel anti-von Willebrand Factor monoclonal antibodies

Von Willebrand Factor is a multimer produced by endothelial cells and megak aryocytes, being stared in intracellular organelles, such as the Weibel-Pal ade bodies and or-granules in endothelial cells and platelets, respectively . This molecule acts as a carrier protein for factor VIIIc, involved in the intrinsic pathway of blood coagulation maintaining its stability in circul ation. Von Willebrand Factor also plays an important role in platelet aggre gation and adhesion to injured vessel wall. It interacts with platelets thr ough two distinct glycoproteins, GPIb and GPIIb/IIIa. We raised two monoclo nal antibodies, ECA-3 and ECA-4, against human umbilical vascular endotheli al cells that recognize and immunoprecipitate van Willebrand Factor. Intere stingly , ECA-4 monoclonal antibody is able to completely inhibit platelet agglutination induced by ristocetin, suggesting that it binds to von Willeb rand Factor close to platelet GPIb binding site, The use of monoclonal anti bodies to identify van Willebrand Factor binding regions to factor VIII or platelets has been reported by others. In pulmonary hypertension, abnormali ties have been detected on the multimeric structure of the molecule as well as on its proteolytic fragments, by using monoclonal antibodies. Moreover, monoclonal antibodies raised against specific regions of von Willebrand Fa ctor molecule may allow studies of functional abnormalities of this protein in inherited and acquired disorders like subtypes of van Willebrand's dise ase. (C) 2000 Elsevier Science Ltd. All rights reserved.