Cytotoxic and morphologic profile of endogenous and pyrimidinone-activated murine NK cells

We investigated the effect of therapeutically relevant pyrimidinone molecules on murine natural killer (NK) cell cytotoxicity. Our studies demonstrated that pyrimidinones augmented or induced substantial levels of NK cell anti-YAC-1-directed cytotoxic potential in the spleen, bone marrow, peripheral blood, peritoneal exudate, lungs, and liver of adult and infant mice. The NK cell stimulating effect of pyrimidinones was not restricted to a single mouse strain, but was displayed by six different inbred strains of mice. Percoll density gradient separation studies demonstrated that activated effector cells were of low density, displayed morphology of large granular lymphocytes (LGL), and expressed asialo GM-1 cell surface antigen. The analysis of the mechanism of NK cell potentiation showed that the increase in the cytotoxic activity was manifested on several levels, including an increased kinetics of lysis and an increase in the number of LGL and in their tumor-binding and killing capacity. Furthermore, the pyrimidinone-mediated NK cell-augmenting effect was abolished by anti-interferon serum, indicating the role of interferon in NK cell potentiation. In the light of possible role of NK cells in cancer defense, pyrimidinones may have therapeutic value in defense against primary and metastatic tumors.