Fig. 2: MLKL-dependent necroptosis is driving hemorrhage in C8-endo mice.
From: Endothelial Caspase-8 prevents fatal necroptotic hemorrhage caused by commensal bacteria
a Micrographs (a) and quantitation (b) of cleaved Caspase-3 staining in the small bowel of a wild-type mouse 15 hours after TNF administration (WT + TNF), a control mouse (C8-flox) and a C8-endo mouse 16 days after starting tamoxifen treatment. Micrographs show the remodeled intestinal wall before (pre-bleed) and after hemorrhage (bleed) in C8-endo mice. Arrows indicate cleaved Caspase-3 in crypts. Asterisk indicates cleaved Caspase-3 within a hemorrhage. b Data are mean ± s.d. from n = 10 for WT + TNF; n = 2 for C8-flox and n = 3 for C8-endo. Over 100 villi were analyzed per mouse. Symbols represent individual mice. c The proportion of mice that became moribund and required euthanasia. Gray boxes indicate days of tamoxifen administration. Data are from one cohort (n = 4–5 mice per group) and representative of 3 independent experiments. ***p < 0.001 via Log-rank Mantel–cox test. d Lengths of the small intestine from matched control (C8-flox) mice, C8-endo-Mlklko mice and moribund C8-endo mice (same cohort as in c). Data are mean ± s.e.m. *p < 0.05 via one-way ANOVA with Holm-Sidak’s multiple comparison test. Symbols represent individual mice. e H&E-stained sections of mice 16 days after starting tamoxifen treatment. f Histopathological scores of H&E-stained sections of the small intestine from moribund C8-endo and matched C8-endo-Mlklko mice. Data are mean ± s.e.m. **p < 0.01 via unpaired two-sided t-test. Symbols represent individual mice.
