Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana Unidad Xochimilco, Calzada del Hueso No. 1100, CP 04960, México DF Mexico.
Int Immunopharmacol. 2012 Jan;12(1):1-9. doi: 10.1016/j.intimp.2011.11.002. Epub 2011 Nov 18.
Lactoferrin (Lf), a multifunctional protein of the innate immune response, seems to act as a permeabilizing agent of Gram negative bacteria, apparently due to its interaction with enterobacterial lipopolysaccharide (LPS) on the bacterial surface. In both human and bovine Lf, a six residue sequence lying in an 18-loop region of the lactoferricin domain is key to Lf-LPS binding. There is much evidence that, by its action on LPS, Lf destabilizes the bacterial membrane and therefore increases bacterial permeability. By itself, Lf is not an effective antibacterial agent, but it permits the penetration of the bacterial membrane by some antibacterial substances whose hydrophobicity otherwise limits their efficacy. Additionally, Lf neutralizes free LPS by keeping the latter from forming complexes that activate TLR-4 signaling pathways. Such pathways, when over-activated, lead to the abundant production of pro-inflammatory mediators such as tumor necrosis factor (TNF) with fatal consequences to the host. The effect of Lf in reducing inflammation and destabilizing Gram negative bacteria has clinical implications in the control of sepsis, multiple organ dysfunction and bacterial invasion.
乳铁蛋白（Lf）是先天免疫反应的多功能蛋白，似乎可以作为革兰氏阴性菌的通透剂，这显然是由于其与细菌表面的肠杆菌脂多糖（LPS）相互作用。在人乳铁蛋白和牛乳铁蛋白中，位于乳铁肽结构域 18 环区域的 6 个残基序列是 Lf-LPS 结合的关键。有大量证据表明，Lf 通过其对 LPS 的作用使细菌膜不稳定，从而增加细菌通透性。Lf 本身并不是一种有效的抗菌剂，但它允许一些疏水性限制其功效的抗菌物质穿透细菌膜。此外，Lf 通过阻止 LPS 形成激活 TLR-4 信号通路的复合物来中和游离 LPS。当这些通路过度激活时，会导致大量促炎介质（如肿瘤坏死因子（TNF））的产生，对宿主造成致命后果。Lf 减轻炎症和破坏革兰氏阴性菌的作用在控制败血症、多器官功能障碍和细菌入侵方面具有临床意义。
