Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes.
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.
Rauova
Lubica
L
Center for Autoimmune Diseases, Department of Medicine B, Sheba Medical Center, Tel Hashomer, Israel.
Gilburd
Boris
B
Zurgil
Naomi
N
Blank
Miri
M
Guegas
Larisa L
LL
Brickman
Chaim M
CM
Cebecauer
Ladislav
L
Deutsch
Mordechai
M
Wiik
Allan
A
Shoenfeld
Yehuda
Y
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
D019268:Antibodies, Antineutrophil Cytoplasmic; D009195:Peroxidase; D012697:Serine Endopeptidases; D053146:Myeloblastin