Treatment with anti-C5a l-aptamer NOX-D19 protected mice from development of pneumonia-induced liver injury. Mice were transnasally infected with Streptococcus pneumoniae (S. pn.; 5 × 106 colony-forming units/mouse) or sham-infected with phosphate-buffered saline, and intraperitoneally treated with NOX-D19 or solvent at time of infection (0 h) and 24 h postinfection. (A and B) Twenty-four hours or 48 h after infection, liver sections were stained for caspase 3A (A) or fibrin (B) and counterstained with hemalaun. In the S. pneumoniae–infected, solvent-treated group, liver necrosis (asterisks) surrounded by caspase 3a–positive apoptotic cells (arrows, A) and fibrin deposition (arrows, B) was seen 48 h postinfection. Liver injury and concomitant microcirculatory failure were absent under NOX-D19 treatment. (C) Forty-eight hours after infection, liver aspartate aminotransferase (AST) quantified in plasma was reduced after NOX-19 treatment, while blood urea nitrogen (BUN) concentrations in plasma were not altered upon treatment. (A and B) Representative images are shown for each group (n = 8). Scale bar = 100 µm (valid for all photomicrographs). (C) Data are represented as boxplots depicting median, quartiles and range; for AST n = 13 (sham, S. pn./solvent) or n = 10 (S. pn./NOX-D19); for BUN n = 12 (sham) or n = 10 (S. pn./solvent) or n = 8 (S. pn./NOX-D19). **P < 0.01, ****P < 0.0001 vs. sham-infected, solvent-treated group, #P < 0.05 vs. S. pneumoniae–infected, solvent-treated group (multiple Mann–Whitney U tests with Bonferroni correction).
