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 c...

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Bibliographic Details
Published in:Clinical immunology (Orlando, Fla.) Fla.), 2003-02, Vol.106 (2), p.139-147
Main Authors: Jiang, Ning, Reich, Charles F, Monestier, Marc, Pisetsky, David S
Format: Article
Language:English
Subjects:
Adjuvants, Immunologic - pharmacology
Animals
Antibodies, Monoclonal - pharmacology
Apoptosis
Apoptosis - drug effects
Apoptosis - physiology
Biological and medical sciences
CpG Islands
Dexamethasone - pharmacology
DNA
Enzyme-Linked Immunosorbent Assay
Fas
fas Receptor - drug effects
fas Receptor - immunology
Female
Fluorescent Dyes - analysis
General aspects
Immunopathology
Immunosuppressive Agents - pharmacology
Lipopolysaccharides - pharmacology
LPS
Lupus Erythematosus, Systemic - blood
Lupus Erythematosus, Systemic - pathology
Lymphocyte Activation
Medical sciences
Mice
Mice, Inbred BALB C
Mice, Inbred C3H
Mice, Inbred MRL lpr
Nucleosomes
Organic Chemicals
Spleen - cytology
Spleen - drug effects
Systemic lupus erythematosus
Thymus Gland - cytology
Thymus Gland - drug effects
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Summary: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.
ISSN:1521-6616
1521-7035
DOI:10.1016/S1521-6616(02)00027-X