de la Rosa Gonzalo, Yang De, Tewary Poonam, Varadhachary Atul, Oppenheim Joost J
Laboratory of Molecular Immunoregulation, Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Fredrick, MD 21702, USA.
J Immunol. 2008 May 15;180(10):6868-76. doi: 10.4049/jimmunol.180.10.6868.
Lactoferrin is an 80-kDa iron-binding protein present at high concentrations in milk and in the granules of neutrophils. It possesses multiple activities, including antibacterial, antiviral, antifungal, and even antitumor effects. Most of its antimicrobial effects are due to direct interaction with pathogens, but a few reports show that it has direct interactions with cells of the immune system. In this study, we show the ability of recombinant human lactoferrin (talactoferrin alfa (TLF)) to chemoattract monocytes. What is more, addition of TLF to human peripheral blood or monocyte-derived dendritic cell cultures resulted in cell maturation, as evidenced by up-regulated expression of CD80, CD83, and CD86, production of proinflammatory cytokines, and increased capacity to stimulate the proliferation of allogeneic lymphocytes. When injected into the mouse peritoneal cavity, lactoferrin also caused a marked recruitment of neutrophils and macrophages. Immunization of mice with OVA in the presence of TLF promoted Th1-polarized Ag-specific immune responses. These results suggest that lactoferrin contributes to the activation of both the innate and adaptive immune responses by promoting the recruitment of leukocytes and activation of dendritic cells.
乳铁蛋白是一种80 kDa的铁结合蛋白，在牛奶和中性粒细胞颗粒中高浓度存在。它具有多种活性，包括抗菌、抗病毒、抗真菌甚至抗肿瘤作用。其大部分抗菌作用是由于与病原体直接相互作用，但有一些报道表明它与免疫系统细胞有直接相互作用。在本研究中，我们展示了重组人乳铁蛋白（α-乳运铁蛋白（TLF））趋化单核细胞的能力。此外，将TLF添加到人类外周血或单核细胞来源的树突状细胞培养物中会导致细胞成熟，这可通过CD80、CD83和CD86表达上调、促炎细胞因子的产生以及刺激同种异体淋巴细胞增殖的能力增强来证明。当注入小鼠腹腔时，乳铁蛋白也会引起中性粒细胞和巨噬细胞的显著募集。在TLF存在的情况下用OVA免疫小鼠可促进Th1极化的抗原特异性免疫反应。这些结果表明，乳铁蛋白通过促进白细胞募集和树突状细胞活化，有助于先天免疫反应和适应性免疫反应的激活。
