title: Two-phase antithrombotic protection after anti-glycoprotein VI treatment in mice.
abstract: OBJECTIVE
  Collagen and thrombin are the strongest physiological platelet agonists, acting through different receptors, among which glycoprotein VI (GPVI) and protease-activated receptors, respectively, are the essential ones. In mice, targeting of GPVI with the monoclonal antibody JAQ1 induces depletion of the receptor from circulating platelets, resulting in abolished collagen responses and long-lasting antithrombotic protection.
  
  
  RESULTS
  Mice were treated with JAQ1, and the early effects of this treatment were analyzed. In addition to the known abolition of the collagen reactivity, this treatment also affected platelet response to thrombin but not other agonists. In platelets from JAQ1-treated mice, thrombin-induced activation of integrin alphaIIbbeta3, the surface expression of P-selectin, and the procoagulant activity were decreased on days 1 and 2, then progressively recovered and returned to normal on day 5. In parallel, the mice were transiently protected from lethal tissue factor-induced pulmonary thromboembolism (100% survivors versus 40% in control group), which appeared to be based on a decreased generation and activity of intravascular thrombin.
  
  
  CONCLUSIONS
  Anti-GPVI treatment induces 2-phase antithrombotic protection in mice consisting of a partial and transient inhibition of thrombin responses in platelets and a prolonged and complete loss of the collagen response.
authors: Rudolf-Virchow-Zentrum, DFG-Forschungszentrum für Experimentelle Biomedizin der Universität Würzburg, Germany.
authors: Valerie
authors: V
authors: Schulte
authors: H Peter
authors: HP
authors: Reusch
authors: Miroslava
authors: M
authors: Pozgajová
authors: David
authors: D
authors: Varga-Szabó
authors: Christian
authors: C
authors: Gachet
authors: Bernhard
authors: B
authors: Nieswandt