Fulminant MAS in mice after injection with TLR9 agonist, CpG, and DG leads to the activation of plasminogen/plasmin. (A) CpG and DG were administered intraperitoneally into 8-week-old female C57BL/6 mice at days 0, 2, 4, 7, 9, 11, 14, 16, 18, and 21 (0h, 48h, 96h, 168h, …). (B) Survival rate of PBS- (n = 10), DG- (n = 10), CpG- (n = 10), or CpG/DG-injected mice (n = 25). (C) Wright-Giemsa–stained slides of peripheral blood, BM, and spleen cells of CpG/DG-injected mice at day 10 show engulfment of erythrocytes in macrophages, so-called hemophagocytosis. Bar represents 20 μm. (D-F) (D) Counts of white blood cells (WBC), (E) red blood cells (RBC), and (F) platelets (Plt) of PBS-, DG-, CpG-, or CpG/DG-injected mice at day 10 (n = 5-7 per group). (G) Number of mononuclear cells in spleens of PBS-, DG-, CpG-, or CpG/DG-injected mice at day 10 (n = 5-7 per group). (H) Representative images of hematoxylin-and-eosin (H&E)–stained sections of the liver from PBS-, DG-, CpG-, or CpG/DG-injected mice at day 10. Bars represent 200 μm. Black dotted lines indicate mononuclear cell infiltration; black arrows, hepatocellular degeneration. (I) Representative images of H&E-stained sections of the BM from PBS-, DG-, CpG-, or CpG/DG-injected mice at day 10. Bars represent 200 μm. (J) Plasma PAP levels of untreated mice, DG-, CpG-, or CpG/DG-injected mice at 2 hours and 50 hours (n = 5-7 per group). (K) Plasma levels of total tPA of untreated mice and CpG/DG-injected mice 50 hours after CpG/DG injection (n = 5-6 per group). (L) Plasma levels of total uPA of untreated mice and CpG/DG-injected mice 50 hours after CpG/DG injection (n = 5-6 per group). Data represent mean ± SEM. *P < .05, **P < .01, ***P < .001, using 1-way ANOVA with the Tukey posttest or the unpaired, 2-tailed Student t test for significance and using the log-rank test for survival curves.