Figure 7.

A1ATM₃₈₃S-CF improves survival in the cecal slurry injection preclinical model of neonatal sepsis. (A) We compared survival of C57BL/6 mouse pups (7-10 days following birth) treated intraperitoneally 1 hour before and 4 hours after intraperitoneal cecal slurry injection (1.3 mg/g mouse body weight) with A1ATM₃₈₃S-CF (N = 16; 10 mg/kg mouse body weight; red dashed line), SCR peptide control (N = 11; 10 mg/kg; red solid line), or DNase 1 (N = 14; 3 mg/g; NET dismantler; green solid line). Cl-amidine (N = 14; 40 mg/g; NET inhibitor; blue solid line) was injected 1 hour before intraperitoneal cecal slurry injection. Vehicle-treated control pups are denoted by the blue dashed line (N = 16). (B) Peritoneal fluid NET formation was assessed 3 hours after cecal slurry injection in 7- to 10-day old C57BL/6 mouse pups ± pretreatment with A1ATM₃₈₃S-CF or SCR peptide control (1 hour; 10 mg/kg; intraperitoneal injection). NET formation was quantitated in the peritoneal fluid using the myeloperoxidase-DNA (MPO-DNA) ELISA. The y-axis depicts NETs: MPO-DNA complexes (optical density [OD] values − background). (C) We compared survival in the cecal slurry injection model of neonatal sepsis between 4- to 6-day old HTRA1^+/+ littermate controls (N = 13; blue dashed line) and HTRA1^−/− mouse pups (N = 11; solid red line). (D) We compared survival of HTRA1^−/− mouse pups treated intraperitoneally 1 hour before and 4 hours after cecal slurry injection with A1ATM₃₈₃S-CF (N = 7; 10 mg/kg mouse body weight; blue dashed line) or SCR peptide control (N = 7; 10 mg/kg; red solid line). *P < .05, **P < .01, ***P < .001. ns, no significant difference according to the log-rank (Mantel-Cox) statistical tool.