Figure 2.
Figure 2. Plasmin inhibitor treatment prevents MAS-associated lethality and tissue destruction. (A) Experimental schedule for the induction of MAS using CpG/DG intraperitoneal injections, and cotreatment with the plasmin inhibitor YO-2 starting from day 0 or from day 4. (B) Survival rate of CpG/DG-injected mice treated with PBS (n = 20) or YO-2 with treatment starting on day 0 (day 0∼; n = 15) or day 4 (day 4∼; n = 15). (C) PAP levels were determined at indicated time points in plasma samples of control and CpG/DG-injected mice coinjected with PBS or YO-2 (n = 5-10 per group). (D) Percentage of WBC, RBC, and Plt in CpG/DG-injected mice treated with PBS or YO-2 (day 0∼) at day 10 (n = 10 per group) (set as 100% for day 0). (E) Spleen cell counts at day 10 of untreated and CpG/DG-injected mice administered with PBS or YO-2 (day 0∼) (n = 7 per group). (F) Representative images of H&E-stained BM sections of untreated and CpG/DG-injected mice treated with PBS or YO-2 (day 0∼) at day 10. Scale bars = 200 μm. Right panel, Total number of BM nucleated cells per femur (n = 5 per group). (G) Representative images of H&E-stained liver sections from untreated and CpG/DG-injected mice treated with PBS/carrier or YO-2 (day 0∼) at day 10. Scale bars = 200 μm. Black dotted lines indicate mononuclear cell infiltration; black arrows, hepatocellular degeneration. Right panel, Histopathological liver score in groups of these mice (n = 5 per group). Cell infiltration: none = 0, mild = 1, moderate = 2, severe = 3. Liver damage: none = 0, mild = 1, moderate = 2, severe = 3. (H) Plasma ferritin levels of untreated mice and CpG/DG-injected mice injected with PBS or YO-2 at day 10 (n = 5 per group). (I) Plasma triglyceride levels of untreated mice and CpG/DG-injected mice treated with PBS or YO-2 at day 10 (n = 5 per group). (J) Plasma TAT levels of untreated mice and CpG/DG-injected mice treated with PBS or YO-2 50 hours after CpG/DG injection (n = 5 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. BMNC, bone marrow nucleated cells; i.p., intraperitoneally.

Plasmin inhibitor treatment prevents MAS-associated lethality and tissue destruction. (A) Experimental schedule for the induction of MAS using CpG/DG intraperitoneal injections, and cotreatment with the plasmin inhibitor YO-2 starting from day 0 or from day 4. (B) Survival rate of CpG/DG-injected mice treated with PBS (n = 20) or YO-2 with treatment starting on day 0 (day 0∼; n = 15) or day 4 (day 4∼; n = 15). (C) PAP levels were determined at indicated time points in plasma samples of control and CpG/DG-injected mice coinjected with PBS or YO-2 (n = 5-10 per group). (D) Percentage of WBC, RBC, and Plt in CpG/DG-injected mice treated with PBS or YO-2 (day 0∼) at day 10 (n = 10 per group) (set as 100% for day 0). (E) Spleen cell counts at day 10 of untreated and CpG/DG-injected mice administered with PBS or YO-2 (day 0∼) (n = 7 per group). (F) Representative images of H&E-stained BM sections of untreated and CpG/DG-injected mice treated with PBS or YO-2 (day 0∼) at day 10. Scale bars = 200 μm. Right panel, Total number of BM nucleated cells per femur (n = 5 per group). (G) Representative images of H&E-stained liver sections from untreated and CpG/DG-injected mice treated with PBS/carrier or YO-2 (day 0∼) at day 10. Scale bars = 200 μm. Black dotted lines indicate mononuclear cell infiltration; black arrows, hepatocellular degeneration. Right panel, Histopathological liver score in groups of these mice (n = 5 per group). Cell infiltration: none = 0, mild = 1, moderate = 2, severe = 3. Liver damage: none = 0, mild = 1, moderate = 2, severe = 3. (H) Plasma ferritin levels of untreated mice and CpG/DG-injected mice injected with PBS or YO-2 at day 10 (n = 5 per group). (I) Plasma triglyceride levels of untreated mice and CpG/DG-injected mice treated with PBS or YO-2 at day 10 (n = 5 per group). (J) Plasma TAT levels of untreated mice and CpG/DG-injected mice treated with PBS or YO-2 50 hours after CpG/DG injection (n = 5 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. BMNC, bone marrow nucleated cells; i.p., intraperitoneally.

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