In vitro inhibition of natural-killer-mediated lysis by chromatin fragments
| Autor: | Gilbert J. Fournié, Toutain Pl, Le Lann Ad, Boissier L, Hervé Benoist |
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| Rok vydání: | 1994 |
| Předmět: |
Cytotoxicity
Immunologic Cancer Research Programmed cell death Immunology Population Biology Natural killer cell Histones 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Reference Values Neoplasms medicine Cell Adhesion Immunology and Allergy Nucleosome Humans Lymphocytes education Receptor education.field_of_study DNA Neoplasm Molecular biology Chromatin Chromium Radioisotopes 3. Good health Nucleosomes Killer Cells Natural medicine.anatomical_structure Histone Oncology chemistry 030220 oncology & carcinogenesis biology.protein DNA 030215 immunology |
| Zdroj: | Cancer immunology, immunotherapy : CII. 39(3) |
| ISSN: | 0340-7004 |
| Popis: | A qualitative impairment of natural killer (NK) function and the presence of circulating DNA have been independently reported in clinical situations such as cancer and lupus. The existence of receptors for chromatin fragments at the leukocyte membrane raised the question of the relation between the presence of chromatin fragments in the extracellular medium and the impairment of NK function. The present study shows that plasmas from patients with metastatic cancer and with pathological DNA concentrations inhibited significantly the NK activity of normal lymphocytes as compared to cancer plasmas with DNA concentrations in the normal range. In vitro, it was demonstrated that chromatin fragments inhibited the NK-mediated cytotoxicity in a dose-dependent manner. Inhibitory concentrations of nucleosomes (2.5-10 micrograms/ml) were lower than those of DNA and histones alone (100 micrograms/ml). Inhibitory effects of nucleosomes, DNA and histones differed also according to the effector population used: nucleosomes were effective whatever the CD56+ cell enrichment of the effector population, while DNA inhibition needed T cells, and histone inhibition probably resulted from a subtoxic effect, prevented by the presence of adherent cells. Finally we found that nucleosomes could inhibit the NK function only when they were present in the extracellular medium. Taken together, these data suggest that the persistence of nucleosomal DNA at sites of cell death or in the blood might be responsible, at least partly, for the NK activity impairment observed in pathological circumstances characterized by a high rate of cell death phenomena such as cancer. |
| Databáze: | OpenAIRE |
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