Structural and Functional Glycobiology Unit, UMR 8576 CNRS-USTL, IFR 147, Bâtiment C9, Université des Sciences et Technologies de Lille, 59655 Villeneuve d'Ascq cedex, France.
Biometals. 2010 Jun;23(3):365-76. doi: 10.1007/s10534-010-9297-1. Epub 2010 Feb 9.
Lactoferrin (Lf) is an essential element of innate immunity, which refers to antigen-nonspecific defense mechanisms that a host uses immediately or within hours after exposure to an antigen. Following infection, Lf is released from neutrophils (PMNs) in blood and inflamed tissues and, such as other soluble pattern-recognition receptors of the innate immunity, Lf recognizes unique microbial molecules called pathogen-associated molecular patterns (PAMPs): LPS from the gram-negative cell wall and bacterial unmethylated CpG DNA. However, unlike classical PAMPs receptors involved in the activation of immune cells, Lf may act either as a competitor for these receptors or as a partner molecule, depending on the physiological status of the organism. These immunomodulatory properties are explained by the ability of Lf to interact with proteoglycans and receptors on the surface of mammalian cells: cells of the innate (NK cells, neutrophils, macrophages, basophils, neutrophils and mast cells) and adaptive [lymphocytes and antigen-presenting cells (APCs)] immune systems, and also epithelial and endothelial cells. Through these interactions, Lf is able to modulate the migration, maturation and functions of immune cells, and thus to influence both adaptive and innate immunities. The understanding of the roles of the host-expressed Lf in immunity comes from in vivo and in vitro studies with exogenous Lf which, although informative, rarely reflect the pathological, or non-pathological, conditions in the organism. In this review, the data from the literature will be critically analyzed in order to present a real picture of the regulatory roles of host Lf in immunity.
乳铁蛋白（Lf）是先天免疫的重要组成部分，它是指宿主在接触抗原后立即或数小时内使用的非抗原特异性防御机制。感染后，Lf 从血液和炎症组织中的中性粒细胞（PMN）中释放出来，与先天免疫的其他可溶性模式识别受体一样，Lf 识别称为病原体相关分子模式（PAMPs）的独特微生物分子：革兰氏阴性细胞壁的 LPS 和细菌未甲基化的 CpG DNA。然而，与参与免疫细胞激活的经典 PAMP 受体不同，Lf 可能作为这些受体的竞争者或伴侣分子发挥作用，这取决于生物体的生理状态。Lf 能够与哺乳动物细胞表面的糖胺聚糖和受体相互作用，从而解释了其免疫调节特性：先天免疫系统（NK 细胞、中性粒细胞、巨噬细胞、嗜碱性粒细胞、中性粒细胞和肥大细胞）和适应性免疫系统[淋巴细胞和抗原呈递细胞（APCs）]的细胞，以及上皮细胞和内皮细胞。通过这些相互作用，Lf 能够调节免疫细胞的迁移、成熟和功能，从而影响适应性免疫和先天免疫。宿主表达的 Lf 在免疫中的作用的理解来自于外源性 Lf 的体内和体外研究，尽管这些研究提供了信息，但很少反映生物体中的病理或非病理条件。在这篇综述中，将批判性地分析文献中的数据，以呈现宿主 Lf 在免疫中的调节作用的真实情况。
