Neutrophil Functions of Patients With Vasculitis Related to Myeloperoxidase-Specific Anti-Neutrophil Antibody

Abstract

Neutrophils are hypothesized to cause tissue damage resulting in the development of vasculitis and glomerulonephritis, although they are known to primarily take part in host defense functions. The infiltration of inflammatory cells. notably neutrophils and macrophages, is observed in the progression of vasculitis. Neutrophils with activated status and anti-neutrophil cytoplasmic antibodies (ANCAs), especially myeloperoxidase-specific (MPO)-ANCA, have been implicated in the development of vasculitis. The target molecule of MPG-ANCA is a lysosomal enzyme MPO that usually acts to kill bacteria, viruses, and fungi and that causes damage to the tissue due to the toxicity of its product, hypochlorite (OCl-). To elucidate the role of MPO-ANCA in the progression of vasculitis, a set of MPO-peptide fragments has been developed, and the corresponding epitope site for the specific monoclonal and/or oligoclonal antibody resulting in vasculitis has been determined. Recently some mouse models have been used for analyzing the correlation between MPO and MPO-ANCA in relation to damage of blood vessels followed by the development of vasculitis. This review focuses on the role of activated neutrophils in the development of vasculitis associated with MPO-ANCA and the target molecules of ANCA. In addition, the reactivities of ANCA and inflammatory cytokines involving leukocyte-derived chemotaxin 2 (LECT2) are also discussed.

The Presence of Anti-Lactoferrin Antibodies in a Subgroup of Eosinophilic Granulomatosis with Polyangiitis Patients and Their Possible Contribution to Enhancement of Neutrophil Extracellular Trap Formation

“…NET components, including MPO, which can mediate the generation of hypochlorite (OCl − ) (21), histones (22), and matrix metalloproteinases (MMP), particularly MMP-2 and MMP-9 (23), have been demonstrated as strong effectors that induced vascular endothelial cell damage. In fact, the presence of extracellular MPO and NET-related molecules, such as histones, has been shown in the glomerular lesions of AAV (10, 24, 25).…”

Neutrophils efficiently cross-prime naive T cells in vivo

“…Moreover, activated neutrophil infiltration in an inflammatory site is associated with some autoimmune disorders such as vasculitis. 44 It therefore appeared crucial to determine whether neutrophils are involved in cross-tolerance or cross-priming. Our observations that neutrophils cross-present antigens to naive T cells in vitro and that Ova-pulsed neutrophils induce naive OT1 CD8 ϩ T-cell proliferation in vivo were not sufficient to speculate about a role for neutrophils in cross-tolerance versus cross-priming.…”

Chemistry and Biology of Angiitis Inducer, Candida albicans Water‐Soluble Mannoprotein‐β‐Glucan Complex (CAWS)

“…This disease results in occasionally fatal sequelae such as the formation of aneurysms in the coronary arteries. Although the current standard treatment regimen consists of administration of large doses of globulin preparations, this approach is not always satisfactory (10,44). Murata et al conducted an analysis on children with Kawasaki disease and found that C. albicans extract (CADS) isolated from the stool specimens of the patients induced coronary angiitis in mice that resembled Kawasaki disease (8,24,25).…”