Attenuation of agonist-induced platelet activation. Human platelets were allowed to circulate in NOD/SCID mice in the presence of monovalent Fab fragments specific for either PECAM-1 (black bars/•) or GPVI (gray bars/▿) for 24 hours and examined for PAC-1 binding induced by (A) 2.5 ng/mL CRP or a cocktail made up of 10 U/mL thrombin + 10 μM ADP + 100 μM epinephrine, or by increasing doses of (B) ADP, (C) thrombin, or (D) CRP. Percentages indicate reduction of PAC-1 binding to human platelets that circulated in the presence of anti-GPVI Fab compared with those that circulated with anti–PECAM-1 Fab. Human platelets were distinguished from murine platelets by their ability to bind the human GPIIb-IIIa complex-specific mAb, AP2. Note that treatment with the anti-GPVI Fab fragment, 6B12, results in generalized loss of agonist-induced platelet activation, an effect that is most pronounced in response to the GPVI-specific agonist CRP.