FIG 6 .

Inhibition of inflammatory cytokine release and neutrophil responses by C5aR1 blockade in lepirudin-anticoagulated human whole-blood infection with N. meningitidis. (A) IL-8 in human whole blood infected with 10⁶ CFU/ml N. meningitidis MC58 in the presence of C5aR1 antagonist (C5aRAs) PMX53 or W-54011 (means ± SEM; n = 5 donors). (B) IL-8 in human whole blood infected for the indicated durations with 10⁶ CFU/ml N. meningitidis MC58 in the presence of PMX53 (10 µM) or W-54011 (300 nM) (means ± SEM; n = 15 donors). (C) Cytokines at 90 min of infection of human whole blood with 10⁶ CFU N. meningitidis MC58 (means ± SEM; n = 16 donors). (D) Oxidative burst measured by DHR123 fluorescence in neutrophils during infection of whole human blood. (E) Neutrophil degranulation during whole-blood infection by surface localization of CD11b normalized to “no C5aRA.” (F) Phagocytosis of MC58-GFP by PMNs in whole blood as determined by flow cytometry and expressed as percentages of PMNs with an increase in the level of FL1-H above the level measured for the noninfected control. (G) N. meningitidis viability in blood of donors with or without C5aRAs. (D to F) Infection with 10⁷ CFU/ml of N. meningitidis MC58; lines indicate medians. (D to G) PMX53 was used at 10 µM and W-54011 at 300 nM. (A–G) *, P < 0.05; **, P < 0.01; ***, P < 0.001 (in repeated-measure ANOVA; matched observations per individual donor).