FIGURE 2. Prophylactic treatment of WT or fibrinogen-deficient mice with fibrinogen γ′ improves survival following septicemia challenge.

(A) Purified total phFib, phFibγ-γ, and phFibγ′-γ were analyzed by SDS-PAGE and Coomassie staining (left) and western blot analysis for the fibrinogen γ′ chain (right). (B) ELISA analysis of citrate plasma collected at various time points from C57Bl/6 mice that were injected with 2 mg of phFibγ-γ or phFibγ′-γ (n=3 mice per time point for each fibrinogen). (C) Model of prophylactic human fibrinogen treatment followed by intravenous infection with S. aureus USA300 in mice. (D) Fga^−/− mice (n=7 per group) were either untreated or injected with 6 mg of phFibγ-γ or phFibγ′-γ followed by retroorbital infection with 1×10⁹ CFUs of S. aureus USA300, and survival was monitored over time. Data were analysed by Kaplan-Meier log-rank analysis, with ^##p < .01 for untreated vs phFibγ′-γ and ***p < .001 phFibγ-γ vs phFibγ′-γ. (E) WT mice (n=10 per group) were untreated or injected with 6 mg of phFibγ-γ or phFibγ′-γ followed by retroorbital infection with 5×10⁸ CFUs of S. aureus, and survival was monitored over time. Data were analyzed by Kaplan-Meier log-rank analysis with ^#p < .05 for untreated vs phFibγ′-γ and *p < .05 for phFibγ-γ vs phFibγ′-γ. (F) Fgg^WT/Δ5 and Fga^−/− mice treated with phFibγ-γ or phFibγ′-γ (n=6–7 mice per group) were injected with 5×10⁸ CFUs of S. aureus USA300, and survival was monitored over time. Data were analyzed by Kaplan-Meier log-rank analysis with ^#p < .05 for Fgg^WT/Δ5 vs phFibγ′-γ.