C5 and Sepsis: This hypothesis is based on previous evidence showing that: (a) C5a/C5aR1 signaling directly triggered neutrophil activation (e.g., granule enzyme release and superoxide anion production/respiratory burst) in several pathological conditions (66–71); (b) C5aR1 signaling induced neutrophils to degranulate — with increase in CD66 expression — in sepsis models (72); (c) C5a levels in the soluble fraction of sputum correlated positively with markers associated with worse cystic fibrosis lung disease, including NE levels, MPO activity, and DNA concentration (73).