The expression of plasma nucleosomes in mice undergoing in vivo apoptosis.
Nucleosomes occur in the blood of patients with systemic lupus erythematosus and are thought to result from in vivo cell death. To determine the conditions for the release of nucleosomes into the blood, normal mice were treated with four agents that have the potential to induce apoptosis or immune cell activation in vivo: LPS, CpG DNA, anti-Fas antibody, and dexamethasone. Blood nucleosomes were measured by a capture ELISA immunoassay, with the DNA component assessed by fluorimetry with the dye PicoGreen. Following treatment with LPS and a monoclonal anti-Fas antibody, nucleosomes and DNA appeared in the plasma in a dose-dependent fashion. In contrast, dexamethasone treatment, despite causing significant thymocyte loss, did not elicit plasma nucleosomes. Similarly, CpG DNA, while inducing an IL-12 response comparable to that of LPS, also did not elicit plasma nucleosomes. These results suggest that plasma nucleosome levels reflect specific patterns of cell death and are not an invariable consequence of in vivo apoptosis or immune cell activation.
Jiang
Ning
N
Division of Rheumatology, Duke University Medical Center, Durham, NC 27709, USA.
Reich
Charles F
CF
Monestier
Marc
M
Pisetsky
David S
DS
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D018899:CpG Islands; D003907:Dexamethasone / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005456:Fluorescent Dyes / Q000032:analysis; D007166:Immunosuppressive Agents / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000473:pathology; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D019463:Mice, Inbred MRL lpr; D009707:Nucleosomes; D009930:Organic Chemicals; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects; D019014:fas Receptor / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D005456:Fluorescent Dyes; D007166:Immunosuppressive Agents; D008070:Lipopolysaccharides; D009707:Nucleosomes; D009930:Organic Chemicals; C099476:PicoGreen; D019014:fas Receptor; D003907:Dexamethasone