Glycoprotein Ib (GPIb)-dependent and GPIb-independent pathways of thrombin-induced platelet activation

Blood. 1991 Apr 15;77(8):1740-8.


In this study, the question of whether glycoprotein Ib (GPIb) mediates both high and moderate affinity pathways of alpha-thrombin-induced platelet activation was examined. Flow cytometric studies, using a panel of monoclonal antibodies (MoAbs), showed that Serratia marcescens protease treatment removed greater than 97% of the glycocalicin portion of GPIb but did not affect the changes in the expression of GPIX or GMP-140 that were induced by high concentrations of alpha-thrombin (10 nmol/L). However, Serratia treatment almost completely abolished the increase in platelet surface GMP-140 induced by low concentrations of alpha-thrombin (0.5 nmol/L) and diminished the downregulation of platelet surface GPIX by 60.9% +/- 5.6% (mean +/- SEM, n = 3). When present in 20-fold molar excess, an MoAb directed against the alpha-thrombin/von Willebrand factor (vWf) binding domains of GPIb completely blocked the ristocetin-dependent binding of vWf to platelets but inhibited only to about 50% the binding of alpha-thrombin and the activation-dependent binding of vWf. In platelets treated with Serratia marcescens protease to remove GPIb, a concentration of this MoAb 16,000-fold in excess of the maximum possible remaining copies of GPIb failed to inhibit platelet activation by alpha-thrombin. These studies demonstrate that activation of intact platelets by alpha-thrombin proceeds by both GPIb-dependent and GPIb-independent mechanisms.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antibodies, Monoclonal
  • Binding Sites
  • Blood Platelets / drug effects
  • Blood Platelets / physiology*
  • Endopeptidases / pharmacology
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Platelet Activation / drug effects*
  • Platelet Membrane Glycoproteins / isolation & purification
  • Platelet Membrane Glycoproteins / physiology*
  • Serratia marcescens / enzymology
  • Thrombin / pharmacology*
  • Thrombin / physiology
  • von Willebrand Factor / physiology


  • Antibodies, Monoclonal
  • Platelet Membrane Glycoproteins
  • von Willebrand Factor
  • Endopeptidases
  • Thrombin