title: Anti-neutrophil cytoplasm antibodies can recognize vascular endothelial cell-bound anti-neutrophil cytoplasm antibody-associated autoantigens.
abstract: Anti-neutrophil cytoplasm antibodies (ANCA) are strongly associated with the development of systemic vasculitis. Myeloperoxidase and proteinase-3 have been identified as targets for P-ANCA and C-ANCA, respectively. Both enzymes are released from neutrophil azurophil granules following neutrophil activation and both are highly cationic. Purified myeloperoxidase is demonstrated to bind non-convalently to endothelial cell membranes, to retain its enzymic function following binding, and to retain its antigenicity for P-ANCA. Endothelial cell-bound myeloperoxidase enhances complement-dependent cytotoxicity of some P-ANCA sere that also contain anti-endothelial cell antibodies. Studies using purified proteinase-3 show that it also can bind to endothelial cells and be recognized by C-ANCA. The interactions of myeloperoxidase and proteinase-3 with endothelial cells and ANCA may thus contribute to the development of vascular injury in patients with systemic vasculitis.
authors.affiliation: Section of Vascular Biology, Royal Postgraduate Medical School, London, UK.
authors.forename: C O
authors.initials: CO
authors.lastname: Savage
authors.forename: G
authors.initials: G
authors.lastname: Gaskin
authors.forename: C D
authors.initials: CD
authors.lastname: Pusey
authors.forename: J D
authors.initials: JD
authors.lastname: Pearson
mesh_terms: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D002478:Cells, Cultured; D003165:Complement System Proteins / Q000276:immunology; D003593:Cytoplasm / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005455:Fluorescent Antibody Technique; D014890:Granulomatosis with Polyangiitis / Q000209:etiology / Q000276:immunology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D053146:Myeloblastin; D009504:Neutrophils / Q000201:enzymology / Q000276:immunology*; D009195:Peroxidase / Q000276:immunology / Q000494:pharmacology; D010488:Polyarteritis Nodosa / Q000209:etiology / Q000276:immunology; D012697:Serine Endopeptidases / Q000276:immunology
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D001323:Autoantibodies; D001324:Autoantigens; D003165:Complement System Proteins; D006861:Hydrogen Peroxide; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin