Figure 3. Requirement for caspase-11 expressed in nonhematopoietic cells in mediating endotoxemia-induced acute lung vascular injury and mortality.

(A) Lung microvessel filtration coefficient (a measure of lung vascular permeability) was determined in WT and Casp11^–/– mice, and the data points depicting individual mice are shown. Mice were exposed to systemic LPS (40 mg/kg i.p.) for 6 hours. Statistics obtained from 2-tailed Student’s t test.(B) H&E-stained cross section of the lung from control mice and LPS-exposed mice at 6 hours shows interstitial edema (indicated by arrows) in WT but not in Casp11^–/– mice. Scale bars: 100 μm. V, lung microvasculature. Images are representative of 5 animals. Quantitative analysis for leukocyte infiltration in lungs (C) and lung tissue MPO activity (D). *P < 0.05; **P < 0.01; ***P < 0.001. Statistics in C and D obtained from ANOVA. (E) Survival of Casp1/11^DKO mice and Casp1^–/– Casp11^Tg mice subjected to a lethal dose of LPS (40 mg/kg i.p.) was assessed and is presented as a Kaplan-Meier plot. (F) Casp11^–/– mice underwent BM irradiation and transplantation with WT BM to reconstitute caspase-11 in hematopoietic cells. Global Casp11^–/– mice as well as Casp11^–/–mice transplanted with WT hematopoietic-lineage cell (BMT) chimeras were protected from lethal sepsis, while nontransplanted WT control mice were not.