Fig. 2

NET upregulation of platelet aggregation is mediated by neutrophil DNA and platelet RAGE. Removing DNA from NET supernatant using DNase I treatment prior to exposure to whole blood reversed the treatment effects of NET supernatant on platelet aggregation in human blood (a, 25.9 ± 2.2 vs. 11.35 ± 0.31, n = 4, p < 0.05). In vivo treatment with DNase I resulted in decreased aggregation in tumor bearing mice (b, AUC 22.1 ± 2.3 vs. 38.4 ± 2.1, n = 4, p < 0.05). Tumor bearing RAGE KO mice have decreased platelet aggregation compared to WT mice (c, AUC 30.6 ± 1.5 vs. 40.2 ± 5.5, n = 4, p < 0.05). Blood from RAGE knockout mice had decreased aggregation after treatment with 100 μL of NET supernatant compared with WT (d, AUC 25.5 ± 2.6 vs. 43.3 ± 3.9, n = 4, p < 0.05). *p < 0.05