Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.
Hussain, Abdullah A K
Price-Kuehne, Fiona E
Savage, Caroline O
Little, Mark A
Salama, Alan D
Klein, Nigel J
Brogan, Paul A
AffiliationInfectious Diseases and Microbiology Unit, 30 Guilford Street, London WC1N 1EH, United Kingdom. firstname.lastname@example.org
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Antibodies, Antineutrophil Cytoplasmic
Intercellular Adhesion Molecule-1
Reactive Oxygen Species
MetadataShow full item record
CitationAnti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. 2012, 23 (1):49-62 J. Am. Soc. Nephrol.
JournalJournal of the American Society of Nephrology : JASN
AbstractThe mechanisms by which anti-neutrophil cytoplasmic antibodies (ANCAs) may contribute to the pathogenesis of ANCA-associated vasculitis are not well understood. In this study, both polyclonal ANCAs isolated from patients and chimeric proteinase 3-ANCA induced the release of neutrophil microparticles from primed neutrophils. These microparticles expressed a variety of markers, including the ANCA autoantigens proteinase 3 and myeloperoxidase. They bound endothelial cells via a CD18-mediated mechanism and induced an increase in endothelial intercellular adhesion molecule-1 expression, production of endothelial reactive oxygen species, and release of endothelial IL-6 and IL-8. Removal of the neutrophil microparticles by filtration or inhibition of reactive oxygen species production with antioxidants abolished microparticle-mediated endothelial activation. In addition, these microparticles promoted the generation of thrombin. In vivo, we detected more neutrophil microparticles in the plasma of children with ANCA-associated vasculitis compared with that in healthy controls or those with inactive vasculitis. Taken together, these results support a role for neutrophil microparticles in the pathogenesis of ANCA-associated vasculitis, potentially providing a target for future therapeutics.
- Increased membrane expression of proteinase 3 during neutrophil adhesion in the presence of anti proteinase 3 antibodies.
- Authors: Brachemi S, Mambole A, Fakhouri F, Mouthon L, Guillevin L, Lesavre P, Halbwachs-Mecarelli L
- Issue date: 2007 Aug
- Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens.
- Authors: Savage CO, Gaskin G, Pusey CD, Pearson JD
- Issue date: 1993 May-Jun
- Tissue factor expression in neutrophil extracellular traps and neutrophil derived microparticles in antineutrophil cytoplasmic antibody associated vasculitis may promote thromboinflammation and the thrombophilic state associated with the disease.
- Authors: Kambas K, Chrysanthopoulou A, Vassilopoulos D, Apostolidou E, Skendros P, Girod A, Arelaki S, Froudarakis M, Nakopoulou L, Giatromanolaki A, Sidiropoulos P, Koffa M, Boumpas DT, Ritis K, Mitroulis I
- Issue date: 2014 Oct
- Anti-myeloperoxidase antibodies enhance phagocytosis, IL-8 production, and glucose uptake of polymorphonuclear neutrophils rather than anti-proteinase 3 antibodies leading to activation-induced cell death of the neutrophils.
- Authors: Hsieh SC, Yu HS, Cheng SH, Li KJ, Lu MC, Wu CH, Tsai CY, Yu CL
- Issue date: 2007 Feb
- Pathogenesis of ANCA-associated vasculitis.
- Authors: Flint J, Morgan MD, Savage CO
- Issue date: 2010 Aug