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 GPIb alpha (rGPIb alpha) (rGPIa/IIa-Ib alpha-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-Ib alpha-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 E1 (PGE), but not by a peptide containing arginine-glycine-glutamic acid (RGE-peptide). In a homogeneous solution, rGPIa/IIa-Ib alpha-liposomes and Fbg-liposomes enhanced platelet aggregation in a dose-dependent manner, as evaluated using an aggregometer. These findings suggest that rGPIa/IIa-Ib alpha-liposomes and Fbg-liposomes form aggregates at the site of injury in blood vessels, resulting in stationary adhesion together with activated platelets.
Nishiya
T
T
Department of Internal Medicine, Keio University, Tokyo, Japan.
Kainoh
M
M
Murata
M
M
Handa
M
M
Ikeda
Y
Y
D015703:Antigens, CD / Q000378:metabolism; D001792:Blood Platelets / Q000378:metabolism*; D001802:Blood Substitutes / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism*; D006801:Humans; D039421:Integrin alpha2; D008081:Liposomes / Q000378:metabolism*; D010973:Platelet Adhesiveness; D010974:Platelet Aggregation; D011994:Recombinant Proteins / Q000378:metabolism
D015703:Antigens, CD; D001802:Blood Substitutes; D006023:Glycoproteins; D039421:Integrin alpha2; D008081:Liposomes; D011994:Recombinant Proteins; D005340:Fibrinogen; D003094:Collagen