Natural killer activity enhancing substance in normal human serum

We studied the effect of normal human serum on natural killer (NK) activity of normal peripheral lymphocytes. Both fresh serum and heat-inactivated (56 degrees C, 30 min) serum significantly enhanced NK activity, in a dose dependent manner, the limit being reached with a final concentration of 5%. However, antibody dependent cell-mediated cytotoxicity (ADCC) was not affected by heat-inactivated serum, although it did show the effects of fresh serum as complement. The serum absorbed with target cells also enhanced NK activity, so it indicated that the enhancing effect of normal serum was not due to the natural antibody against target cells in the serum. The serum was fractionated by Sephadex G-200 into fractions I, II and III in the order of elution. The enhancing factor existed in fraction III. When fraction III was further separated by Cibacron Blue-Sepharose, which selectively adsorbs albumin from serum, the enhancing activity existed in the albumin-rich subfraction. In addition, commercial human albumins had the NK enhancing activity, whereas native transferrin, platelet-derived growth factor (PDGF) or plasminogen did not. These results therefore suggest that the substance enhancing NK activity in normal serum is serum albumin, which is considered to have no significant effect on immune reaction.