Fig 1: Pharmacological blockade of NETs synergizes with Fn14 mAb to confer protection against AKI elicited by abdominal sepsis dependent of macrophages. (A) Experimental scheme of SIVE (100 mg/kg) or ITEM-2 (0.5 mg) monotherapy and SIVE plus ITEM-2 combination therapy for CLP mice with or without intraperitoneal anti-CSF1R (300 µg) pretreatment [-/+] at the indicated time points. (B) Kaplan-Meier curves analyzing survivals of mice with intraperitoneal administration of SIVE, ITEM-2 or both in the absence [-] or presence [+] of anti-CSF1R pretreatment at the indicated times after CLP challenge. Log-rank t test was used to caculate the P value. (C and D) Representative pictures (C) and quantification (D) of H&E staining in renal sections from CLP mice with intraperitoneal administration of SIVE, ITEM-2 or both in the absence [-] or presence [+] of anti-CSF1R pretreatment. Data are expressed as mean ± s.d. **P < 0.01 and ***P < 0.001, one-way ANOVA, post hoc comparisons, Tukey's test. Scale bar: 50 µm. (E and F) Representative pictures (E) and quantification (F) of NGAL staining in renal sections from CLP mice with intraperitoneal administration of SIVE, ITEM-2 or both in the absence [-] or presence [+] of anti-CSF1R pretreatment. Data are expressed as mean ± s.d. *P < 0.05, one-way ANOVA, post hoc comparisons, Tukey's test. Scale bar: 50 µm. (G and H) Serum creatinine (Scr, G) and blood urea nitrogen (BUN, H) levels in CLP mice with intraperitoneal administration of SIVE, ITEM-2 or both in the absence [-] or presence [+] of anti-CSF1R pretreatment. Data are expressed as mean ± s.d. **P < 0.01 and ***P < 0.001, one-way ANOVA, post hoc comparisons, Tukey's test. (I-L) ELISA assays determining serum concentration of HMGB1 (I), IL-1β (J), TNF (K) and IL-6 (L) in CLP mice with intraperitoneal administration of SIVE, ITEM-2 or both in the absence [-] or presence [+] of anti-CSF1R pretreatment. Data are expressed as mean ± s.d. **P < 0.01 and ***P < 0.001, one-way ANOVA, post hoc comparisons, Tukey's test.