C5 and endothelial dysfunction: Neutrophils activated by antineutrophil cytoplasmic antibodies adhere to the endothelial cell, leading to activation of the endothelium and increased vascular permeability. Activated neutrophils release toxic granules, causing direct endothelial cell injury and fibrinoid necrosis through an increase in reactive oxygen species, proteases, and neutrophil extracellular traps. There is activation of the alternative complement pathway with amplification of inflammation through the recruitment of anaphylatoxins, especially C5a, leading to greater endothelial dysfunction (14, 73, 92).