Role of macrophages in the generation of circulating blood nucleosomes from dead and dying cells.

Published

Journal Article

After apoptosis or necrosis, macrophages clear dead cells by phagocytosis. Although this process is efficient, circulating nucleosomes can occur in certain diseases, presumably reflecting either increased production or impaired clearance. To investigate the generation of blood nucleosomes, graded numbers of apoptotic and necrotic cells were administered to healthy mice, and levels of blood nucleosomes and DNA were determined. Using Jurkat cells as a model, nucleosomes and DNA were detected in the blood after the administration of 108 apoptotic or necrotic cells per mouse by the intraperitoneal route. The kinetics of the response were similar for both types of cells. The role of macrophages was assessed by eliminating these cells with clodronate liposomes or silica. Although clodronate treatment alone produced a peak level of blood DNA, the subsequent administration of dead cells caused no change in DNA levels. In contrast, silica treatment alone did not elicit a blood DNA response, though this treatment limited the rise in DNA from administered cells. Molecular studies showed that the blood DNA following the administration of apoptotic or necrotic cells arose from the mouse and the Jurkat cells, and its size distribution was consistent with apoptosis. Together, these findings suggest that the generation of blood nucleosomes depends on macrophages, with apoptosis a concomitant of a high burden of dead and dying cells.

Full Text

Duke Authors

Cited Authors

  • Jiang, N; Reich, CF; Pisetsky, DS

Published Date

  • September 15, 2003

Published In

Volume / Issue

  • 102 / 6

Start / End Page

  • 2243 - 2250

PubMed ID

  • 12775567

Pubmed Central ID

  • 12775567

International Standard Serial Number (ISSN)

  • 0006-4971

Digital Object Identifier (DOI)

  • 10.1182/blood-2002-10-3312

Language

  • eng

Conference Location

  • United States