Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

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.

DOI: 10.1681/ASN.2011030298

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@article{Hong2012AntineutrophilCA, title={Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.}, author={Ying Hong and Despina Eleftheriou and Abdullah A K Hussain and Fiona E Price-Kuehne and Caroline O. S. Savage and David R. W. Jayne and Mark Alan Little and Alan David Salama and Nigel Klein and Paul A Brogan}, journal={Journal of the American Society of Nephrology : JASN}, year={2012}, volume={23 1}, pages={49-62} }