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

Biomaterials. 2011 Aug;32(23):5365-70. doi: 10.1016/j.biomaterials.2011.04.011. Epub 2011 May 6.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adsorption
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / pharmacology
  • Circular Dichroism
  • Fatty Alcohols / chemistry
  • Fibrinogen / chemistry
  • Fibrinogen / metabolism*
  • Gold / chemistry
  • Humans
  • Platelet Adhesiveness / drug effects
  • Platelet Adhesiveness / physiology*
  • Platelet Glycoprotein GPIIb-IIIa Complex / antagonists & inhibitors
  • Platelet Glycoprotein GPIIb-IIIa Complex / metabolism*
  • Platelet Glycoprotein GPIb-IX Complex / antagonists & inhibitors
  • Platelet Glycoprotein GPIb-IX Complex / immunology
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*
  • Platelet Membrane Glycoproteins / metabolism
  • Protein Conformation
  • Protein Structure, Secondary
  • Serum Albumin / chemistry
  • Serum Albumin / metabolism*
  • Silicones / chemistry
  • Sulfhydryl Compounds / chemistry
  • Tirofiban
  • Tyrosine / analogs & derivatives
  • Tyrosine / pharmacology

Substances

  • 11-mercaptoundecanol
  • Antibodies, Monoclonal
  • Fatty Alcohols
  • Platelet Glycoprotein GPIIb-IIIa Complex
  • Platelet Glycoprotein GPIb-IX Complex
  • Platelet Membrane Glycoproteins
  • Serum Albumin
  • Silicones
  • Sulfhydryl Compounds
  • dodecylmercaptan
  • Tyrosine
  • Gold
  • Fibrinogen
  • Tirofiban