Ligand interactions with the RGD recognition site alter binding of GPIIb-IIIa reactive monoclonal antibody to human platelets.
A major component of thrombus formation is the activation of blood platelets and binding of soluble fibrinogen. Glycoprotein IIb-IIIa (GPIIb-IIIa) is the dominant receptor on platelets mediating this activity. This study describes how GPIIb-IIIa is differentially displayed on resting and activated human platelets and how this display is alternatively masked and enhanced by arginine-glycine-aspartic acid (RGD) containing or mimicking compounds. Results indicate that thrombin strongly increases GPIIb-IIIa display on platelet membrane surfaces while other platelet activators enhance GPIIb-IIIa display to lesser degrees. This upregulated display was masked by compounds RGDS, GPenGRGDSPCA and L-367,073. Conversely, membrane GPIIb-IIIa display was markedly enhanced on otherwise resting platelets by incubation with these same compounds. This study indicates that small ligands that bind to RGD recognition sites can modulate GPIIb-IIIa membrane surface display differentially, depending on the nature of their cellular targets.
Lilly Research Laboratories, Indianapolis, Indiana 46285.
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D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001792:Blood Platelets / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism* / Q000494:pharmacology*; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D013917:Thrombin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
D000911:Antibodies, Monoclonal; D009842:Oligopeptides; D010980:Platelet Membrane Glycoproteins; C047981:arginyl-glycyl-aspartic acid; D013917:Thrombin