Nucleosome-dependent escape of tumor cells from natural-killer-mediated lysis: nucleosomes are taken up by target cells and act at a postconjugation level |
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Authors: | A-D Le Lann-Terrisse Gilbert Jean Fournié Hervé Benoist |
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Institution: | Department of Cell Physiology and Hematology, UFR de Pharmacie, Université de Reims Champagne-Ardenne, F-51096 Reims cedex, France Fax (33)3?–?26?–?05?–?35?–?45, FR Institut National de la Santé et de la Recherche Médicale (INSERM)- U 28, H?pital Purpan, Université Paul Sabatier, Toulouse, France, FR Institut National de la Santé et de la Recherche Médicale INSERM-CJF 9206, H?pital Rangueil, Université Paul Sabatier, Toulouse, France, FR
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Abstract: | Our previous data suggested that chromatin fragments released from dead cells into the extracellular medium could be involved
in the impairment of natural-killer (NK)-mediated cytotoxicity reported in cancer patients. In the present study, an inhibition
of the NK-mediated lysis was obtained in vitro by nucleosome addition to different tumor target cells, independently of their
sensitivity to NK-mediated lysis. We observed a rapid endocytosis and degradation of nucleosomes by K562 tumor target cells
and (although to a much lesser extent) a binding to a subpopulation of lymphocytes. Nucleosomes impaired neither the conjugation
step nor the expression of adhesion molecules at the effector (CD11a, CD18, CD2) or target (CD54, CD58) cell surface. On the
contrary, flow-cytometry analysis of the conjugation suggested that nucleosomes might stabilize the conjugates. Investigations
of the killing process showed that nucleosomes decreased the NK cytotoxic potential without modifying Ca2+-dependent lethal-hit-delivery kinetics. The cytotoxic potential was not restored by increasing the available magnesium and
calcium concentrations in the extracellular medium. Taken together, the results suggest that the inhibition of NK-mediated
lysis by nucleosomes may result from alterations of the NK mechanism at the postconjugation level and after lethal-hit delivery.
Hence, the inhibition could involve a delay in the recycling of effector cells, or a resistance of tumor target cells to NK
cells.
Received: 7 October 1996 / Accepted: 12 November 1996 |
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Keywords: | Natural killer lymphocyte Cell death Nucleosome Endocytosis Tumor resistance |
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