Anti-Neutrophil Cytoplasmic Antibodies Stimulate Release of Neutrophil Microparticles

Research output: Contribution to journalArticle

Authors

  • Y Hong
  • D Eleftheriou
  • AAK Hussain
  • FE Price-Kuehne
  • D Jayne
  • MA Little
  • AD Salama
  • NJ Klein
  • PA Brogan

Colleges, School and Institutes

Abstract

The 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.

Details

Original languageEnglish
Pages (from-to)49-62
Number of pages14
JournalJournal of the American Society of Nephrology
Volume23
Issue number1
Publication statusPublished - 1 Jan 2012