Nucleosome is a necrosis inducer for lymphocytes: consequences in systemic lupus erythematosus
© BioMed Central Ltd 2001
Received: 15 January 2001
Published: 26 January 2001
Nucleosome is a major autoantigen in systemic lupus erythematosus. It is composed of DNA (multiple of 180 bp) and the five histones H1, H2A, H2B, H3 and H4. Previous works have shown the presence of circulating nucleosome in sera of lupus patients, which could be due to increased apoptosis or impaired phagocytosis, both resulting in secondary necrosis and release of nucleosome. On the other hand, it was shown that nucleosome could bind to the surface of cells, such as lymphocytes. In order to better understand the role of this circulating complex, we analysed the effect of purified nucleosome on living murine lymphocytes. Here we show that nucleosome induces necrosis of cells, and not apoptosis, as assessed by different techniques. Similar results were obtained with mono-, di-, tri- and poly-nucleosomes. Moreover, this effect is time and dose dependent, is impaired when nucleosome is heat-inactivated and is not observed with other non related purified proteins. Finally, we analysed in more details the sensitivity of B and T cells to nucleosome. These results suggest that nucleosomes released by apoptotic cells could induce necrosis of neighbouring cells, thus allowing the release of cell contents in high amounts. This phenomenon would act as an "amplification loop" and could explain how the peripheral tolerance is broken and is in agreement with inflammatory responses which are normally not associated with apoptosis.