Antiinflammatory, antiapoptotic, and mortality reduction activities of E149A-APC. (A) APC antiinflammatory activity determined as inhibition of IL-6 secretion of LPS-challenged U937 cells by wt-hAPC (□), E149A-hAPC (◇), and 5A-hAPC (○). (B) Inhibition of staurosporine-induced EAhy926 endothelial cell apoptosis by wt-hAPC (□), E149A-hAPC (◇), 5A-hAPC (○), and catalytically inactive S360A-hAPC (×). Apoptosis is expressed relative to that observed in the absence of added APC. Each point represents the mean plus or minus SEM of at least 3 independent experiments. (C) Survival of mice given an LD₉₀ dose of endotoxin via intraperitoneal (IP) injection, followed by immediate treatment with E149A-mAPC (10 μg (■, solid line), 2 μg (▴, hatched line), or PBS control ●). Animals treated with 10 μg of E149A-mAPC showed significantly increased mortality (P < .05 by log-rank test) compared with PBS-treated mice. (D) Survival of mice given an LD₉₀ dose of endotoxin via IP injection, followed by immediate treatment with 5A-mAPC (10 μg (■, solid line), 2 μg (▴, hatched line), or PBS control ●). Animals treated with 2 μg or 10 μg of 5A-mAPC showed significantly increased survival (P < .05 by log-rank test) compared with PBS-treated mice. (E) Survival of mice given an LD₉₀ dose of endotoxin and treated with wt-mAPC (10 μg (■, solid line), 2 μg (▴, hatched line), or 0.2 μg (♦, dotted line) compared with PBS (●) alone treatment. Animals treated with 2 μg or 10 μg of wt-mAPC showed significant increased survival (P < .05 by log-rank test) compared with PBS-treated mice. (C-E) Animals per group: PBS, n = 20; each APC dose, n = 12.