Characterization of the novel murine monoclonal anti-von Willebrand factor (vWf) antibody GUR76-23 which inhibits vWf interaction with alpha IIb beta 3 but not alpha v beta 3 integrin.
von Willebrand factor (vWf) is known to interact with the two beta 3 integrins, alpha IIb beta 3 and alpha v beta 3, in an RGD-dependent manner. We characterized a novel murine monoclonal antibody to human vWf, GUR76-23, which recognized a site within the carboxy-terminal half of the molecule containing the RGD sequence. This antibody inhibited high shear-induced platelet aggregation and blocked adhesion of ADP plus epinephrine-stimulated platelets to vWf, indicating that it interferes with the interaction with alpha IIb beta 3. Unlike antibodies against the RGD site, however, the antibody was without effect on adhesion of cultured human umbilical vein endothelial cells to vWf, a phenomenon known to involve the interaction with alpha v beta 3. GUR76-23 binding was not displaced by anti-RGD antibodies. These results suggest that the adhesive interaction of vWf with these two beta 3 integrins may be differentially modulated by a site(s) other than the common RGD module.
Yokoyama
K
K
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Handa
M
M
Oda
A
A
Katayama
M
M
Fujimura
Y
Y
Murata
M
M
Kawai
Y
Y
Watanabe
K
K
Ikeda
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000302:isolation & purification / Q000494:pharmacology*; D001667:Binding, Competitive; D002448:Cell Adhesion; D002478:Cells, Cultured; D004587:Electrophoresis, Agar Gel; D004730:Endothelium, Vascular / Q000166:cytology; D000939:Epitopes / Q000276:immunology; D006801:Humans; D015151:Immunoblotting; D007140:Immunoglobulin Fab Fragments / Q000276:immunology / Q000378:metabolism; D051379:Mice; D010446:Peptide Fragments / Q000378:metabolism; D010974:Platelet Aggregation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D019030:Receptors, Vitronectin / Q000378:metabolism*; D012310:Ristocetin / Q000494:pharmacology; D014471:Umbilical Veins; D014841:von Willebrand Factor / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism
D000911:Antibodies, Monoclonal; D000939:Epitopes; D007140:Immunoglobulin Fab Fragments; D010446:Peptide Fragments; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019030:Receptors, Vitronectin; D014841:von Willebrand Factor; D012310:Ristocetin