title: Platelet glycoprotein VI dimerization, an active process inducing receptor competence, is an indicator of platelet reactivity.
abstract: OBJECTIVE
  The immune receptor homologue glycoprotein VI (GPVI)/FcR receptor γ chain complex is primarily responsible for platelet activation by collagen. There is growing evidence that optimal binding of GPVI to collagen depends on the assembly of GPVI dimers. The valence of GPVI on resting platelets needs to be clearly established because platelet avidity for collagen would be greater if GPVI is constitutively expressed as a dimer than as a monomer.
  
  
  RESULTS
  Using a monoclonal antibody (9E18) that preferentially binds to GPVI dimers, we found that GPVI was maintained in a monomeric form on human resting platelets under the control of intraplatelet cAMP concentration. Activation by soluble agonists or von Willebrand factor induced a shift toward GPVI dimerization related to increased platelet adhesion to collagen. A correlation between platelet binding of 9E18 and P-selectin exposure was observed in patients experiencing coronary artery disease, and antagonists of the ADP receptor P2Y12 limited ADP-induced GPVI dimerization.
  
  
  CONCLUSIONS
  The rapid assembly of highly competent dimers of GPVI at sites of vascular lesion represents an important step in the sequence of events leading to platelet activation by collagen. GPVI dimers could represent a new marker to analyze platelet reactivity.
authors.affiliation: INSERM U698, CHU Xavier Bichat, 46 rue Henri Huchard 75877 Paris Cedex 18, France.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Loyau
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Dumont
authors.forename: Véronique
authors.initials: V
authors.lastname: Ollivier
authors.forename: Yacine
authors.initials: Y
authors.lastname: Boulaftali
authors.forename: Laurent
authors.initials: L
authors.lastname: Feldman
authors.forename: Nadine
authors.initials: N
authors.lastname: Ajzenberg
authors.forename: Martine
authors.initials: M
authors.lastname: Jandrot-Perrus
mesh_terms: D000911:Antibodies, Monoclonal / Q000378:metabolism; D000918:Antibody Specificity; D015415:Biomarkers / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D019007:P-Selectin / Q000378:metabolism; D010297:Paris; D015539:Platelet Activation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use; D010980:Platelet Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D055503:Protein Multimerization; D058921:Purinergic P2Y Receptor Antagonists / Q000627:therapeutic use; D058925:Receptors, Purinergic P2Y12 / Q000187:drug effects / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D015415:Biomarkers; D019007:P-Selectin; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D010980:Platelet Membrane Glycoproteins; D058921:Purinergic P2Y Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; C546937:SELP protein, human; C098341:platelet membrane glycoprotein VI; D014841:von Willebrand Factor; D003094:Collagen; D000242:Cyclic AMP