The endogenous EPCR/aPC pathway contributes to protection from lethality in LD50 LPS-challenged mice. (A) Plasma TAT and IL1β levels 18 hours after LD50 LPS challenge in wild-type mice treated at 10 hours with wild-type aPC, aPC5A,⁴⁴  aPC149A, anti-PC antibody (TVM1), or hirudin (mean ± SD; n = 4/group; * indicates different from untreated control; P < .02 by ANOVA). (B) Characterization of antimouse PC antibody (TVM1) dose responses for antibody binding to immobilized mouse PC (top panel) and for inhibition of mouse aPC amidolytic (middle panel) and anticoagulant (bottom panel) activities. (C-E) Survival after intervention with the indicated agents at 10 hours after LD50 intraperitoneal LPS (5 mg/kg) challenge of wild-type (WT) mice (C,D) or PAR1^−/− or EPCR^low mice (E). n = 8–17/group; P < .01 for aPC5A, anti-PC TVM1, or EPCR^low vs WT control.