Fig. 1.

TSG6 deletion in mice (TSG6^−/−) augments LPS-induced inflammatory lung injury. (A and B) WT (TSG6^+/+) and TSG6^−/− mice were challenged with LPS (10 mg/kg i.p.). (A) Lungs obtained at 0, 24 h, and 48 h after LPS challenge were used to measure MPO activity in lungs. (B) After LPS challenge, lung vascular permeability (uptake of EBA) was assessed. n = 4 mice per time point. *P < 0.05, WT vs. TSG6^−/−. (C) Survival of age- and weight-matched WT and TSG6^−/− mice monitored after challenge with a lethal dose of LPS (20 mg/kg i.p.). TSG6^−/− mice showed the highest mortality within 20 h after LPS injection compared with WT mice. n = 10 per group. *P < 0.001, WT vs. TSG6^−/−. (D) Survival of TSG6^−/− mice challenged with LPS (20 mg/kg, i.p.) with and without simultaneous i.t. instillation of TSG6 (5 µg/mouse). TSG6 instillation rescued the high mortality seen in the TSG6^−/− mice, increasing survival by 60% compared with untreated controls. n = 8 mice per group. *P < 0.001. (E and F) WT mice were simultaneously challenged with LPS (10 mg/kg, i.p.) and saline (i.t) or TSG6 (5 µg/mouse, i.t.). (E) At 0 and 24 h after LPS/saline or LPS/TSG6 administration, mice were used for lung EBA permeability measurements as above. Mice treated with TSG6 showed significantly reduced lung vascular permeability compared with untreated control mice. n = 5 mice per group; *P < 0.05, LPS vs. LPS + TSG6. (F) At 0 and 24 h after LPS/saline or LPS/TSG6 administration, lungs were used to measure MPO activity, expressed as change in absorbance (ΔA). MPO activity was significantly reduced in lungs of TSG6-treated mice compared with saline-treated control mice. n = 4 mice per group. *P < 0.05, LPS vs. LPS + TSG6. (G) Survival in WT mice, monitored for 72 h after a lethal dose of LPS (20 mg/kg i.p.) alone or in combination with TSG6 (5 µg/mouse) given i.t. either concomitantly with or 6 h after LPS challenge. n = 10 per group. *P < 0.001, LPS vs. LPS + TSG6; *P < 0.03, LPS vs. LPS + TSG6 post-LPS.