Thrombin decreases von Willebrand factor binding to platelet glycoprotein Ib.
Thrombin is a physiological agonist that promotes platelet aggregation and secretion. In this study we observed that thrombin can also inhibit a function of platelets related to primary hemostasis. Platelet stimulation by thrombin decreased the binding of von Willebrand factor (vWF) to glycoprotein (GP) Ib and decreased ristocetin-induced agglutination, in vitro reactions that correlate with initial platelet adhesion to the vessel wall. Binding of the monoclonal antibody API to GP Ib was also decreased. Cytoskeletal participation in the change of GP Ib was suggested because pretreatment of platelets with cytochalasin to prevent actin filament formation prevented the thrombin-induced decreases in vWF binding. API binding, and ristocetin-induced agglutination. Measurement of GP Ib in detergent extracts by electroimmunoassay demonstrated no loss after thrombin stimulation. Electroimmunoassay also demonstrated that the API epitope of GP Ib on intact thrombin-treated platelets was accessible for complete digestion by chymotrypsin. Therefore GP Ib was neither released from the platelet surface nor internalized by thrombin treatment. A previously recognized effect of thrombin is its induction of receptor sites on platelet surface GP IIb-IIIa for contact-promoting proteins, including vWF that are involved in the platelet spreading and aggregation that follow adhesion. Therefore the action on GP Ib may combine with the effect on GP IIb-IIIa to shift platelet reactivity from GP Ib-vWF-mediated initial contact with the vessel wall to GP IIb-IIIa-mediated spreading and aggregation.
George
J N
JN
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7880.
Torres
M M
MM
D000199:Actins / Q000378:metabolism; D000911:Antibodies, Monoclonal / Q000276:immunology; D001792:Blood Platelets / Q000187:drug effects*; D003571:Cytochalasin B / Q000494:pharmacology; D003864:Depression, Chemical; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D012310:Ristocetin / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology*; D014841:von Willebrand Factor / Q000378:metabolism*
D000199:Actins; D000911:Antibodies, Monoclonal; D010980:Platelet Membrane Glycoproteins; D014841:von Willebrand Factor; D012310:Ristocetin; D003571:Cytochalasin B; D013917:Thrombin