Nishiya K, Horwitz D A
J Immunol. 1982 Dec;129(6):2519-23.
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.
铁及铁结合蛋白乳铁蛋白（LF）对自然杀伤（NK）细胞及抗体依赖的细胞毒性作用（ADCC）具有显著影响。在短期铬释放试验中，将人贴壁和非贴壁血单核细胞与K562细胞及抗体致敏的Chang细胞共同孵育。柠檬酸铁（10⁻³M）抑制贴壁和非贴壁NK细胞活性，但对ADCC无影响。LF显著影响贴壁单核细胞的细胞毒性，但对非贴壁淋巴细胞无影响。LF以剂量依赖方式增强NK细胞活性，但相同浓度却反常地抑制ADCC。LF直接作用于贴壁效应细胞，因为细胞预处理30分钟就足以产生增强作用。铁饱和的LF以及不饱和蛋白均增强贴壁细胞的NK活性。所有测试浓度的转铁蛋白均未改变NK活性。这些研究表明，除了先前描述的作用外，铁对免疫功能还有抑制作用，并揭示了LF的一种新的调节作用。LF对贴壁细胞的选择性作用进一步证明，单核细胞至少在贴壁状态下可具有强大的NK活性。LF对NK和ADCC的相反作用尚无法解释，可能作为一种探究手段来明确其中涉及的机制。
