Reconstitution of adhesive properties of human platelets in liposomes carrying both recombinant glycoproteins Ia/IIa and Ib alpha under flow conditions: specific synergy of receptor-ligand interactions

Liposomes carrying both recombinant glycoprotein Ia/IIa (rGPIa/IIa)and Ib (rGPIb) (rGPIa/IIa-Ib-liposomes) instantaneously and irreversibly adhered to the collagen surface in the presence ofsoluble von Willebrand factor (VWF) at high shear rates, in markedcontrast with translocation of liposomes carrying rGPIb alone onthe VWF surface. In the absence of soluble VWF, the adhesion ofrGPIa/IIa-Ib-liposomes to the collagen surface decreased with increasing shear rates, similar to liposomes carrying rGPIa/IIa alone.While adhesion of liposomes with exofacial rGPIa/IIa and rGPIbdensities of 2.17 × 10³ and 1.00 × 10⁴molecules per particle, respectively, was efficient at high shear rates, reduction in rGPIb density to 5.27 × 10³molecules per particle resulted in decreased adhesion even in thepresence of soluble VWF. A 50% reduction in the exofacial rGPIa/IIadensity resulted in a marked decrease in the adhesive ability of theliposomes at all shear rates tested. The inhibitory effect of antibodyagainst GPIb (GUR83-35) on liposome adhesion was greater at highershear rates. Further, the anti-GPIa antibody (Gi9) inhibited liposomeadhesion more than GUR83-35 at all shear rates tested. These resultssuggest that the rGPIa/IIa-collagen interaction dominates the adhesionof rGPIa/IIa-Ib-liposomes to the collagen surface at low shearrates, while the rGPIa/IIa-collagen and rGPIb-VWF interactioncomplements each other, and they synergistically provide the neededfunctional integration required for liposome adhesion at high shearrates. This study thus has confirmed for the first time the proposedmechanisms of platelet adhesion to the collagen surface under flowconditions using the liposome system.