title: Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes.
abstract: Translocation of intracellular components to the cell surface during the priming or apoptosis of polymorphonuclear leukocytes (PMN) is an important mechanism for interaction of antineutrophil cytoplasmic antibodies (ANCA) with these antigens. To test the capacity of apoptotic PMN to trigger production of ANCA, six groups of mice were immunized with either live or apoptotic lymphocytes, or with live, apoptotic, formalin-fixed, or lysed PMN. Mice immunized with both live and apoptotic neutrophils developed high titers of antibodies which gave a granular cytoplasmic immunofluorescent pattern. These antibodies were specific for lactoferrin and myeloperoxidase. Following a second intravenous infusion of apoptotic PMNs, mice developed anti-PR3 antibodies. Vasculitis lesions were not found in mice which developed ANCA. The ANCA-containing IgG fraction induced superoxide production by human PMNs. These results support the hypothesis that neutrophil-specific antigens presented on the cell membranes of apoptotic PMN may induce ANCA in the proper conditions.
authors: Center for Autoimmune Diseases, Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel.
authors: Lubica
authors: L
authors: Rauova
authors: Boris
authors: B
authors: Gilburd
authors: Naomi
authors: N
authors: Zurgil
authors: Miri
authors: M
authors: Blank
authors: Larisa L
authors: LL
authors: Guegas
authors: Chaim M
authors: CM
authors: Brickman
authors: Ladislav
authors: L
authors: Cebecauer
authors: Mordechai
authors: M
authors: Deutsch
authors: Allan
authors: A
authors: Wiik
authors: Yehuda
authors: Y
authors: Shoenfeld
mesh_terms: D000818:Animals; D019268:Antibodies, Antineutrophil Cytoplasmic / Q000096:biosynthesis*; D017209:Apoptosis; D006801:Humans; D007114:Immunization; D008214:Lymphocytes / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D053146:Myeloblastin; D009504:Neutrophils / Q000276:immunology* / Q000502:physiology; D009195:Peroxidase / Q000097:blood; D016897:Respiratory Burst; D012697:Serine Endopeptidases / Q000097:blood
chemical_list: D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin