Delineating the roles of the GPIIb/IIIa and GP-Ib-IX-V platelet receptors in mediating platelet adhesion to adsorbed fibrinogen and albumin

• Published in: Biomaterials 2011-08, Vol.32 (23), p.5365-5370
• Main Authors: Sivaraman, Balakrishnan, Latour, Robert A
• Format: Article
• Language: English
• Subjects: adhesion; Adsorption; Advanced Basic Science; Albumin; albumins; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; biocompatible materials; Blood compatibility; Circular Dichroism; Dentistry; drugs; Fatty Alcohols - chemistry; Fibrinogen; Fibrinogen - chemistry; Fibrinogen - metabolism; Gold - chemistry; Humans; monoclonal antibodies; Platelet adhesion; Platelet Adhesiveness - drug effects; Platelet Adhesiveness - physiology; Platelet Glycoprotein GPIb-IX Complex - antagonists & inhibitors; Platelet Glycoprotein GPIb-IX Complex - immunology; Platelet Glycoprotein GPIb-IX Complex - metabolism; Platelet Glycoprotein GPIIb-IIIa Complex - antagonists & inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex - metabolism; Platelet Membrane Glycoproteins - metabolism; Protein Conformation; Protein Structure, Secondary; receptors; Serum Albumin - chemistry; Serum Albumin - metabolism; Silicones - chemistry; Sulfhydryl Compounds - chemistry; Thrombosis; Tyrosine - analogs & derivatives; Tyrosine - pharmacology
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2011.04.011

Abstract Platelet adhesion to adsorbed plasma proteins, such as fibrinogen (Fg), has been conventionally thought to be mediated by the GPIIb/IIIa receptor binding to Arg-Gly-Asp (RGD)-like motifs in the adsorbed protein. In previous studies, we showed that platelet adhesion response to adsorbed Fg and Alb was strongly influenced by the degree of adsorption-induced protein unfolding and that platelet adhesion was only partially blocked by soluble RGD, with RGD-blocked platelets adhering without activation. Based on these results, we hypothesized that in addition to the RGD-specific GPIIb/IIIa receptor, which mediates both adhesion and activation, a non-RGD-specific receptor set likely also plays a role in platelet adhesion (but not activation) to both Fg and albumin (Alb). To identify and elucidate the role of these receptors, in addition to GPIIb/IIIa, we also examined the GPIb-IX-V receptor complex, which has been shown to mediate platelet adhesion (but not activation) in studies by other groups. The platelet suspension was pretreated with either a GPIIb/IIIa-antagonist drug Aggrastat® or monoclonal antibodies 6B4 or 24G10 against GPIb-IX-V prior to adhesion on Fg- and Alb-coated OH- and CH3 -functionalized alkanethiol self-assembled monolayer surfaces. The results revealed that GPIIb/IIIa is the primary receptor set involved in platelet adhesion to adsorbed Fg and Alb irrespective of their degree of adsorption-induced unfolding, while the GPIb-IX-V receptor complex plays an insignificant role. Overall, these studies provide novel insights into the molecular-level mechanisms mediating platelet interactions with adsorbed plasma proteins, thereby assisting the biomaterials field develop potent strategies for inhibiting platelet-protein interactions in the design of more hemocompatible cardiovascular biomaterials and effective anti-thrombotic therapies.