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.