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Nucleosomes induce lymphocyte necrosis.

Patrice Decker1, Hartwig Wolburg, Hans-Georg Rammensee

  • 1Institute for Cell Biology, Department of Immunology, University of Tübingen, Auf der Morgenstelle 15, D-72076 Tübingen, Germany. patrice.decker@uni-tuebingen.de

European Journal of Immunology
|July 30, 2003
PubMed
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Nucleosomes cause necrosis in lymphocytes, potentially amplifying systemic lupus erythematosus inflammation. This cell death mechanism was reversed by treating nucleosomes with DNase I, proteinase K, or antibodies.

Area of Science:

  • Immunology
  • Cell Biology

Background:

  • Nucleosomes are key autoantigens in systemic lupus erythematosus (SLE).
  • Circulating nucleosome complexes are present in SLE patients and mice.
  • A potential cell surface receptor for nucleosomes has been proposed but not identified.

Purpose of the Study:

  • To investigate the effects of nucleosome-receptor interactions on target cells.
  • To determine the mechanism of nucleosome-induced cell death.
  • To explore the in vivo relevance of nucleosome-induced effects.

Main Methods:

  • Ex vivo treatment of lymphocytes and dendritic cells with purified nucleosomes.
  • Assessment of cell death via necrosis.
  • In vivo studies involving intravenous injection of nucleosomes in mice.

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Main Results:

  • Purified nucleosomes induced dose- and time-dependent necrosis in lymphocytes, while dendritic cells showed resistance.
  • Nucleosome-induced necrosis was abrogated by deoxyribonuclease I, proteinase K, or a specific monoclonal antibody.
  • Intravenous nucleosome injection in mice led to a reduced spleen cell count.

Conclusions:

  • Nucleosomes directly induce necrosis in lymphocytes, a novel finding.
  • This nucleosome-induced necrosis may contribute to an amplification loop in SLE pathogenesis.
  • The results suggest a potential therapeutic target for managing SLE-related inflammation.