Fig. 5.
Treatment with anti-C5a l-aptamer NOX-D19 protected pulmonary barrier function in combined severe pneumonia and mechanical ventilation without affecting pulmonary leukocyte recruitment. 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 23 h postinfection. One hour later (24 h postinfection), mechanical ventilation was performed for 6 h. Ventilated and nonventilated mice were euthanized 30 h after infection. (A) Human serum albumin was applied 90 min before termination of the experiment, and the human serum albumin concentration in bronchoalveolar lavage fluid (BALF) and plasma determined. The permeability index was defined as the ratio of the human serum albumin concentration in BALF and plasma (x10-3). Lung hyperpermeability induced by pneumonia and mechanical ventilation was lower upon NOX-D19 treatment. (B) Pulmonary leukocyte recruitment was not altered by NOX-D19 treatment. Values are given as mean and SD. In (A), n = 5 (nonventilated) or n = 11 (solvent/ventilated) or n = 10 (NOX-D19/ventilated); in (B), n = 5 (nonventilated) or n = 11 (solvent/ventilated) or n = 10 (sham/NOX-D19/ventilated) or n = 9 (S. pn./NOX-D19/ventilated). **P < 0.01, ***P < 0.001 between indicated groups, ##P < 0.01 v. S. pneumoniae–infected, solvent-treated, ventilated group (one-way ANOVA and Sidak’s multiple comparisons test).