Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.

Hdl Handle:
http://hdl.handle.net/10147/237983
Title:
Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.
Authors:
Hong, Ying; Eleftheriou, Despina; Hussain, Abdullah A K; Price-Kuehne, Fiona E; Savage, Caroline O; Jayne, David; Little, Mark A; Salama, Alan D; Klein, Nigel J; Brogan, Paul A
Affiliation:
Infectious Diseases and Microbiology Unit, 30 Guilford Street, London WC1N 1EH, United Kingdom. y.hong@ich.ucl.ac.uk
Citation:
Anti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. 2012, 23 (1):49-62 J. Am. Soc. Nephrol.
Journal:
Journal of the American Society of Nephrology : JASN
Issue Date:
Jan-2012
URI:
http://hdl.handle.net/10147/237983
DOI:
10.1681/ASN.2011030298
PubMed ID:
22052057
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed?term=Anti-neutrophil%20cytoplasmic%20antibodies%20stimulate%20release%20of%20neutrophil%20microparticles
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.
Item Type:
Article
Language:
en
MeSH:
Adolescent; Animals; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Antibodies, Antineutrophil Cytoplasmic; Antigens, CD18; Autoantigens; Case-Control Studies; Cell-Derived Microparticles; Cells, Cultured; Child; Child, Preschool; Endothelial Cells; Endothelium, Vascular; Female; Humans; Intercellular Adhesion Molecule-1; Interleukin-6; Interleukin-8; Male; Mice; Myeloblastin; Neutrophil Activation; Peroxidase; Reactive Oxygen Species; Thrombin
ISSN:
1533-3450

Full metadata record

DC FieldValue Language
dc.contributor.authorHong, Yingen_GB
dc.contributor.authorEleftheriou, Despinaen_GB
dc.contributor.authorHussain, Abdullah A Ken_GB
dc.contributor.authorPrice-Kuehne, Fiona Een_GB
dc.contributor.authorSavage, Caroline Oen_GB
dc.contributor.authorJayne, Daviden_GB
dc.contributor.authorLittle, Mark Aen_GB
dc.contributor.authorSalama, Alan Den_GB
dc.contributor.authorKlein, Nigel Jen_GB
dc.contributor.authorBrogan, Paul Aen_GB
dc.date.accessioned2012-08-09T13:50:22Z-
dc.date.available2012-08-09T13:50:22Z-
dc.date.issued2012-01-
dc.identifier.citationAnti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles. 2012, 23 (1):49-62 J. Am. Soc. Nephrol.en_GB
dc.identifier.issn1533-3450-
dc.identifier.pmid22052057-
dc.identifier.doi10.1681/ASN.2011030298-
dc.identifier.urihttp://hdl.handle.net/10147/237983-
dc.description.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.en_GB
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed?term=Anti-neutrophil%20cytoplasmic%20antibodies%20stimulate%20release%20of%20neutrophil%20microparticlesen_GB
dc.rightsArchived with thanks to Journal of the American Society of Nephrology : JASNen_GB
dc.subject.meshAdolescent-
dc.subject.meshAnimals-
dc.subject.meshAnti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis-
dc.subject.meshAntibodies, Antineutrophil Cytoplasmic-
dc.subject.meshAntigens, CD18-
dc.subject.meshAutoantigens-
dc.subject.meshCase-Control Studies-
dc.subject.meshCell-Derived Microparticles-
dc.subject.meshCells, Cultured-
dc.subject.meshChild-
dc.subject.meshChild, Preschool-
dc.subject.meshEndothelial Cells-
dc.subject.meshEndothelium, Vascular-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshIntercellular Adhesion Molecule-1-
dc.subject.meshInterleukin-6-
dc.subject.meshInterleukin-8-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMyeloblastin-
dc.subject.meshNeutrophil Activation-
dc.subject.meshPeroxidase-
dc.subject.meshReactive Oxygen Species-
dc.subject.meshThrombin-
dc.titleAnti-neutrophil cytoplasmic antibodies stimulate release of neutrophil microparticles.en_GB
dc.typeArticleen
dc.contributor.departmentInfectious Diseases and Microbiology Unit, 30 Guilford Street, London WC1N 1EH, United Kingdom. y.hong@ich.ucl.ac.uken_GB
dc.identifier.journalJournal of the American Society of Nephrology : JASNen_GB
dc.description.provinceLeinsteren

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