Platelet Interactions With Liposomes Carrying Recombinant Platelet Membrane Glycoproteins Or Fibrinogen: Approach To Platelet Substitutes

Liposomes carrying both recombinant platelet membrane glycoproteins GPIa/IIa (rGPIa/IIa) and GPIbalpha (rGPIbalpha) (rGPIa/IIa-Ibalpha-liposomes), or fibrinogen (Fbg-liposomes) were prepared. Their interactions with platelets on a collagen surface under flow conditions were evaluated using a recirculating flow chamber, mounted on an epifluorescence microscope, which allows for real-time visualization of fluorescence-labeled liposomes or platelets interacting with the surface. Adhesion of platelets to the collagen surface increased with increasing the shear rate from 600 to 2400 s(-1). Also, the percentages of surface coverage of rGPIa/IIa-Ibalpha-liposomes or Fbg-liposomes increased with increasing platelet adhesion. These phenomena were attenuated by a peptide containing arginine-glycine-aspartic acid (RGD-peptide), or prostaglandin E, (PGE), but not by a peptide containing arginine-glycine-glutamic acid (RGE-peptide). In a homogeneous solution, rGPIa/IIa-Ibalpha-liposomes and Fbg-liposomes enhanced platelet aggregation in a dose-dependent manner, as evaluated using an aggregometer. These findings suggest that rGPIa/IIa-Ibalpha-liposomes and Fbg-liposomes form aggregates at the site of injury in blood vessels, resulting in stationary adhesion together with activated platelets.