P-G6 inhibition of platelet-leukocyte aggregation in vitro and in vivo. (A-B) Inhibition of platelet-leukocyte aggregation in vitro. Anticoagulated mouse or human blood was dosed with 120 µM P-G6 or saline control. Platelet-leukocyte aggregation was induced by adding species-specific PAR peptide, and samples were analyzed using flow cytometry to quantify platelet-positive monocytes or neutrophils. P-G6 significantly reduced platelet-leukocyte aggregation in mouse (A) and human (B) blood. Unstimulated control blood is included for reference. (C-F) Inhibition of platelet-leukocyte aggregation in vivo. Intravital microscopy was used to characterize TNF-α–induced venular inflammation. Immediately prior to cremaster exteriorization, mice were infused with P-G6 or saline vehicle control and antiplatelet CD42b-DyLight 649 (red)/antineutrophil Alexa Fluor 488 (green). Platelet fluorescent signal was normalized to vessel area and reported as median integrated fluorescence over time (C) and AUC (D). P-G6 significantly reduced platelet accumulation to adherent neutrophils (E) compared with mice administered saline vehicle (F). Data are mean ± SEM. ***P < .001, *P < .05, Student t test. PMN, polymorphonuclear cells.