Effects of cadmium on cytotoxic functions of human natural killer cells

The effect of cadmium (Cd(2+)) was studied on natural killer (NK) cell-mediated cytotoxicity as well as on antibody-dependent cellular cytotoxicity (ADCC) of human peripheral blood lymphocytes. The results show that cadmium chloride inhibits human NK and ADCC activities against K562 and Ab-coated P815 target cells in a dose- and time-dependent manner. Maximal inhibition (80-90%) was observed in the presence of 100 mum-cadmium chloride, and it does not appear to be due to toxic effects on effector cells. Purification of large granular lymphocytes by Percoll density gradient centrifugation suggests that Cd(2+) acts directly on this cell population. No effects of Cd(2+) could be found after pre-exposure of either effector or target cells separately. The inhibitory effect of Cd(2+) was manifested only when effector and target cells were present simultaneously. The greatest inhibition of NK and ADCC activities occurred when cadmium chloride was added to the assay within the first 60 min, suggesting that an early event was affected by Cd(2+). However, Cd(2+) did not block effector-target conjugate formation or affect leucocyte function associated Ag-1 expression on effector cells. This indicates that an initial triggering of effector cells by target cells was required before Cd(2+) could exert its effect. Cd(2+)-induced inhibition of cytotoxic functions of NK cells could be only partially prevented by increasing the external Ca(2+) concentration or by adding Zn(2+) to the culture medium.