Platelets trigger EET formation. (A) Eosinophils release IL-5 after co-incubation with activated platelets (plt) (n = 8). Resting platelets (n = 8), supernatant (conditioned medium [CM]) of activated platelets (activ. plt) (n = 6), and thrombin (n = 4) had significantly smaller effects on IL-5-secretion of eosinophils. (B) Isolated eosinophils formed EETs containing MBP (arrows) after activation by platelets. EETs were also found in human arterial thrombi and in murine arterial thrombi. Images representative of 5 experiments. (C) Quantification of EETs and NETs in thrombi induced by FeCl₃ in ApoE^−/− mice (n = 5) after 13 weeks of HFD given as percent of total extracellular traps. (D) Eosinophils formed EETs after interaction with activated platelets (n = 8), whereas resting platelets (n = 7), CM (n = 6), and thrombin control (n = 8) lead to significantly less EET formation. (E) Treatment of eosinophils and platelets with a P-selectin blocking antibody before activation inhibited EET formation (n = 7) compared with isotype control (n = 7). (F) Representative images of EET formation. Arrows indicate EETs. (G) CCL5-blocking antibodies failed to reduce EET formation (n = 6) compared with isotype control (n = 6). (H) In vitro experiments with isolated human eosinophils showed that EET formation declined when eosinophils were pretreated with Siglec-8 binding antibodies (n = 5) compared with EET formation in cells treated with isotype control antibodies (n = 7) before activation by platelets. (I) The images show representatively that Siglec-8 binding antibodies prevent EET formation (arrows). For panels A, C-E, and G-H, data are mean ± SD. *P < .05; **P < .01; ****P < .0001. ns, not significant.