title: Delineating the roles of the GPIIb/IIIa and GP-Ib-IX-V platelet receptors in mediating platelet adhesion to adsorbed fibrinogen and albumin.
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 CH(3)-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.
authors.affiliation: Department of Biomedical Engineering, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, United States.
authors.forename: Balakrishnan
authors.initials: B
authors.lastname: Sivaraman
authors.forename: Robert A
authors.initials: RA
authors.lastname: Latour
mesh_terms: D000327:Adsorption; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D002942:Circular Dichroism; D005233:Fatty Alcohols / Q000737:chemistry; D005340:Fibrinogen / Q000737:chemistry / Q000378:metabolism*; D006046:Gold / Q000737:chemistry; D006801:Humans; D010973:Platelet Adhesiveness / Q000187:drug effects / Q000502:physiology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry / Q000378:metabolism*; D012828:Silicones / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000737:chemistry; D000077466:Tirofiban; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: C521238:11-mercaptoundecanol; D000911:Antibodies, Monoclonal; D005233:Fatty Alcohols; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins; D012709:Serum Albumin; D012828:Silicones; D013438:Sulfhydryl Compounds; C013976:dodecylmercaptan; D014443:Tyrosine; D006046:Gold; D005340:Fibrinogen; D000077466:Tirofiban