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Blood, Vol. 93 No. 11 (June 1), 1999:
pp. 3956-3963
Horizontal Transfer of DNA by the Uptake of Apoptotic Bodies
Lars Holmgren,
Anna Szeles,
Eva Rajnavölgyi,
Judah Folkman,
Georg Klein,
Ingemar Ernberg, and
Kerstin I. Falk
From the Center for Genomic Research and Microbiology and Tumor
Biology Center, Karolinska Institute, Stockholm, Sweden; the Department
of Immunology, L. Eötvös University, Göd, Hungary;
and the Department of Surgery, Children's Hospital, and Department of
Cell Biology, Harvard Medical School, Boston, MA.
In this study we have raised the question of whether DNA can be
transferred from one cell to another by phagocytosis of apoptotic bodies. We have used integrated copies of the Epstein-Barr virus (EBV)
as a marker to follow the fate and expression pattern of apoptotic DNA
in the phagocytotic host. Apoptosis was induced in EBV-carrying cell
lines by irradiation before cultivation with either human fibroblasts,
macrophages, or bovine aortic endothelial cells. Analysis of the
expression pattern of EBV-encoded genes was performed by
immunofluorescent staining as well as in situ hybridization.
Cocultivation of apoptotic bodies from lymphoid cell lines containing
integrated but not episomal copies of EBV resulted in expression of the
EBV-encoded genes EBER and EBNA1 in the recipient cells at a high
frequency. Fluorescence in situ hybridization analysis showed uptake of
human chromatin as well as integrated EBV-DNA into the nuclei of bovine
aortic endothelial cells. These data show that DNA may be rescued and
reused from apoptotic bodies by somatic cells. In addition, our
findings suggest that apoptotic bodies derived from EBV-carrying B
lymphocytes may serve as the source of viral transfer to cells that
lack receptors for the EBV virus in vivo.
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