Induction of biologically active antineutrophil cytoplasmic antibodies by immunization with human apoptotic polymorphonuclear leukocytes

Lubica Rauova, Boris Gilburd, Naomi Zurgil, Miri Blank, Larisa L. Guegas, Chaim M. Brickman, Ladislav Cebecauer, Mordechai Deutsch, Allan Wiik, Yehuda Shoenfeld

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)69-78
Number of pages10
JournalClinical Immunology
Volume103
Issue number1
DOIs
StatePublished - 2002
Externally publishedYes

Keywords

  • ANCA
  • Apoptosis
  • Myeloperoxidase
  • Polymorphonuclear leukocytes
  • Proteinase 3
  • Vasculitis

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