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.