Fig. 7: Inhibiting Platelet- or MC activation, or blocking specific MC degranulation products improves mortality in septic shock.

A Mortality after injection of 5×10⁷ colony forming units/ml (CFU) E. coli J96 in WT mice pretreated with either saline or Ticagrelor (n = 5 mice/group). B Mortality after injection of 5×10⁷ CFU E. coli J96 in MC depleted MCPT5-DTA or in non-depleted littermates (n = 5 mice/group). C Mortality in the CLP sepsis model in MC depleted MCPT5-DTA or in non-depleted littermates (n = 5 mice/group). D Rectal temperature measurements in WT or MCPT4^-/- mice after injection of 4 × 10⁸ CFU E. coli J96 (n = 5 mice/group; *p = 0.016, ***p = 0.0009; ****p < 0.0001). E) Intravenous Evans blue extravasation after intradermal injection of recombinant Chymase Mcpt4-TAT (Mcpt4+vehicle; n = 9), saline (n = 4) or inactivated Mcpt4-TAT (Mcpt4+inhibitors; n = 4) as shown in representative images (inserts) and by quantification from ear skin samples. F) Mortality after injection of 5×10⁷ CFU E. coli J96 in animals pretreated with either saline or the Chymase inhibitor Ty51469 (n = 4–9 mice/group). Analyses by Log-rank test, one-sided, unpaired Student’s t test, and two-way ANOVA where appropriate. All data are shown as mean ± SEM. Boxplot outlines the median (central line), the interquartile range (boxes), and 1.5 times the interquartile range (whiskers). Source data are provided as a Source Data file.