Figure 4.
Histone-induced coagulation activation in vivo. (A) Box plot shows the medians of thrombin–anti-thrombin (TAT) levels in 20 healthy donors (Normal) and 52 patients with severe nonthoracic trauma. *Median test, P = 0.001. (B) Mean ± SD of TAT in mice infused with saline (Control), calf thymus histones (Histones, 50 mg/ml), or histones plus anti-histone scFv (ahscFv, 10 mg/kg) (Hist+ahscFv) (10 mice per group). *Analysis of variance (ANOVA) test, P < 0.05 compared with Control and Hist+ahscFv groups. (C) Mean ± SD of TAT in mice treated with anesthetics alone (Control), mice subjected to trauma (Trauma), and mice infused with ahscFv (10 mg/kg) 10 minutes before trauma (Trauma+ahscFv) (10 mice per group). *ANOVA test, P < 0.05 compared with Control and Trauma+ahscFv groups. (D) Tissue sections from (a and c) untreated mice and (b and d) mice infused with a 75-mg/kg concentration of calf thymus histones. (b) Hematoxylin and eosin (H&E)–stained lung section with microvascular thrombi (arrows). (d) H&E-stained kidney section with thrombi (arrow). (E) Immunohistochemical staining of lung sections from (a) an untreated mouse and (b–d) mice after infusion of histones (75 mg/kg). (a and d) Stained with anti-fibrin; (b) stained with secondary antibody only; (c) probed with anti-fibrin preincubated with fibrin (Sigma) as controls. Arrow in d indicates thrombosis in an anti-fibrin–stained lung section. Scale bars: 50 μm.