1. Diagram depicting the pathogenesis of vascular lesions in ANCA vasculitis and GN. The events from left to right occur sequentially at each site of injury, and are repeatedly initiated at multiple sites until induction of remission.
Diagram depicting the pathogenesis of vascular lesions in ANCA vasculitis and GN. The events from left to right occur sequentially at each site of injury, and are repeatedly initiated at multiple sites until induction of remission. Neutrophil priming, for example by cytokines generated by a synergistic infection, primes neutrophils and presents ANCA antigens at the surface and in the microenvironment of neutrophils. ANCA-activated neutrophils adhere to and penetrate vessel walls, and release destructive inflammatory mediators and undergo NETosis. ANCA-activated neutrophils release factors that activate the alternative complement pathway, which generates C5a and amplifies the inflammation by attracting and priming more neutrophils. At sites of vessel wall disruption, plasma spills into the necrotic zone and coagulation factors are activated to produce fibrin, resulting in a fibrinoid necrosis in vessels in tissue and crescents in glomeruli. Leukocytes undergo apoptosis and necrosis producing leukocytoclasia. Within a few days, the acute inflammation and necrosis is replaced by infiltrating macrophages and lymphocytes, and scarring begins as activated fibroblasts and myofibroblasts lay down collagen. (Shown only at the right side of the acute lesion is monocyte activation by ANCA, which is occurring in parallel with neutrophil activation at all sites of acute injury.) NET, neutrophil extracellular trap.
J. Charles Jennette, and Patrick H. Nachman CJASN 2017;12:
©2017 by American Society of Nephrology