Monoclonal antibodies to the glycoprotein IIb-IIIa epitopes involved in adhesive protein binding: effects on platelet spreading and ultrastructure on human arterial subendothelium.
Platelet adherence to subendothelium depends on binding of plasma von Willebrand factor (VWF) to the subendothelial surface and its subsequent interaction with platelet membrane glycoprotein Ib (GPIb) in the Baumgartner perfusion technique. To examine the role of the platelet glycoprotein IIb-IIIa (GPIIb-IIIa) complex in these processes, we performed studies in patients with platelets deficient in GPIIb-IIIa (thrombasthenia) or GPIb (Bernard-Soulier syndrome) in the Baumgartner system with human umbilical artery segments at a wall shear rate of 2600 sec-1. Morphometry specified the percentage of the subendothelial surface covered with contact (C) or spread (S) platelets or platelet thrombi. Total platelet adherence was defined as C + S. In thrombasthenia, C showed a small but significant increase compared with controls, whereas C + S was reduced by approximately 40%; thrombi were totally absent. With Bernard-Soulier platelets, each parameter was reduced by 72% to 93%. To verify that these findings were related to the epitopes involved in VWF, fibronectin, and fibrinogen binding, we incubated normal blood with monoclonal antibodies to the GPIIb-IIIa complex (10E5 and PLT-1) or GPIb (6D1), and these experiments yielded results similar to those observed with thrombasthenic and Bernard-Soulier platelets, respectively. By transmission electron microscopy, normal platelets preincubated with 10E5 or thrombasthenic platelets showed abnormally short and blunt pseudopodia, suggesting that the platelet GPIIb-IIIa complex plays a role in platelet spreading on subendothelium. Our observations confirm that platelet spreading is mediated at least in part by the epitope(s) of the GPIIb-IIIa complex involved in adhesive protein binding.(ABSTRACT TRUNCATED AT 250 WORDS)
D000328:Adult; D000911:Antibodies, Monoclonal; D001158:Arteries; D001606:Bernard-Soulier Syndrome / Q000097:blood; D001792:Blood Platelets / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D004727:Endothelium; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D008875:Middle Aged; D010477:Perfusion; D010973:Platelet Adhesiveness; D010980:Platelet Membrane Glycoproteins / Q000172:deficiency / Q000276:immunology* / Q000502:physiology; D013915:Thrombasthenia / Q000097:blood
D000911:Antibodies, Monoclonal; D000939:Epitopes; D010980:Platelet Membrane Glycoproteins