Lactoferrin acts as an alarmin to promote the recruitment and activation of APCs and antigen-specific immune responses
Lactoferrin acts as an alarmin to promote the recruitment and activation of APCs and antigen-specific immune responses
复制标题
DOI：
10.4049/jimmunol.180.10.6868
复制
发表时间：
2008-05-15
影响因子：
4.4
通讯作者：
Oppenheim, Joost J.
中科院分区：
文献类型：
--
作者：
De la Rosa, Gonzalo;Yang, De;Oppenheim, Joost J.
乳铁蛋白是一种80 kDa的铁结合蛋白，以高浓度存在于牛奶和中性粒细胞颗粒中。它具有多种活性，包括抗菌，抗病毒，抗真菌，甚至抗肿瘤作用。它的大多数抗菌作用是由于与病原体的直接相互作用，但少数报告显示它与免疫系统细胞有直接相互作用。在这项研究中，我们展示了重组人乳铁蛋白（talactoferrin alfa（TLF））化学吸引单核细胞的能力。更重要的是，TLF添加到人外周血或单核细胞来源的树突状细胞培养物中导致细胞成熟，如通过上调CD80、CD83和CD86的表达、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加所证明的。当注射到小鼠腹腔中时，乳铁蛋白还引起中性粒细胞和巨噬细胞的显著募集。在TLF存在下用OVA免疫小鼠促进Thl极化的Ag特异性免疫应答。这些结果表明，乳铁蛋白通过促进白细胞的募集和树突状细胞的活化而有助于先天性和适应性免疫应答的活化。
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 Thl-polarized Ag-specitic 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.