The role of neutrophils in causing antineutrophil cytoplasmic autoantibody-associated vasculitis

Item Type:	Review
Title:	The role of neutrophils in causing antineutrophil cytoplasmic autoantibody-associated vasculitis
Creators Name:	Schreiber, A. and Choi, M.
Abstract:	PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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-1beta) 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-1beta 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. SUMMARY: 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-1beta generation have been recently identified and could lead to better targeted novel therapies.
Keywords:	Antineutrophil Cytoplasmic Antibody, Interleukin-1 beta, NADPH Oxidase, Neutrophil Extracellular Trap Generation, Neutrophil Serine Protease, Animals
Source:	Current Opinion in Hematology
ISSN:	1065-6251
Publisher:	Lippincott Williams & Wilkins
Volume:	22
Number:	1
Page Range:	60-66
Date:	January 2015
Official Publication:	https://doi.org/10.1097/MOH.0000000000000098
PubMed:	View item in PubMed

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