The role of neutrophils in causing antineutrophil cytoplasmic autoantibody-associated vasculitis.
OBJECTIVE
Antineutrophil cytoplasmic antibody (ANCA)-activated phagocytes cause vasculitis and necrotizing crescentic glomerulonephritis. Experimental data support the notion that activation of neutrophils and monocytes by ANCA immunoglobulin G with generation of reactive oxygen species, degranulation of proteases, and formation of neutrophil extracellular traps play a role in tissue injury.


RESULTS
We discuss novel findings regarding the expression of ANCA antigens and the mechanisms involved in myeloid cell activation by ANCA immunoglobulin G. The contribution of neutrophil serine proteases and their specific role in the generation of interleukin-1beta (IL-1β) is highlighted. ANCA-induced reactive oxygen species generation plays an important role in downregulating inflammation by inhibition of the inflammasome-dependent caspase-1 activation and subsequent IL-1β generation. Neutrophil extracellular trap generation by ANCA-activated neutrophils and their potential role in the pathogenesis of the disease will be discussed. Lastly, the pathogenic role of the complement system will be discussed.


CONCLUSIONS
ANCA-induced activation of both neutrophils and monocytes is one of the main pathogenic mechanisms involved in disease induction. Therefore, a better understanding of the fundamental processes involved here are necessary. Specifically, the mechanisms involved in IL-1β generation have been recently identified and could lead to better targeted novel therapies.
aExperimental and Clinical Research Center (ECRC) at the MDC Berlin, Charité Berlin bDepartment of Nephrology and Intensive Care Medicine, Campus Virchow Clinic, Medical Faculty of the Charité, Berlin, Germany.
Adrian
A
Schreiber
Mira
M
Choi
D000818:Animals; D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000276:immunology; D020170:Caspase 1 / Q000378:metabolism; D005921:Glomerulonephritis / Q000276:immunology / Q000473:pathology / Q000628:therapy; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology; D018375:Neutrophil Activation; D009504:Neutrophils / Q000276:immunology* / Q000473:pathology*
D019268:Antibodies, Antineutrophil Cytoplasmic; C508585:IL1B protein, human; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D020170:Caspase 1