Contrasting effects of lactoferrin on human lymphocyte and monocyte natural killer activity and antibody-dependent cell-mediated cytotoxicity.

Iron and the iron-binding protein lactoferrin (LF) have significant effects on natural killer (NK) and antibody-dependent cellular cytotoxicity (ADCC). Human adherent and nonadherent blood mononuclear cells were incubated with K562 cells and antibody-sensitized Chang cells in short-term chromium-release assays. Ferric citrate (10(-3) M) inhibited both adherent and nonadherent NK cell activity, but had no effect upon ADCC. LF markedly affected adherent monocyte cytotoxicity, but had no effect on nonadherent lymphocytes. LF enhanced NK in a dose-dependent manner, but similar concentrations paradoxically inhibited ADCC. LF acted directly upon the adherent effector cell because pretreatment of cells for 30 min was sufficient for enhancement. Fe-saturated LF as well as the unsaturated protein enhanced adherent cell NK. Transferrin in all concentrations tested did not alter NK activity. These studies show inhibitory effects of iron on immune function in addition to those previously described and reveal a new regulatory role for LF. The selective effect of LF on adherent cells provides further evidence that monocytes, at least in the adherent state, can have potent NK activity. The opposite effects of LF on NK and ADCC are unexplained and may serve as a probe to define the mechanisms involved.